EXHIBIT 5.1

SICHENZIA ROSS FRIEDMAN FERENCE LLP

61 Broadway, 32nd Floor

New York, NY 10006

Telephone: (212) 930-9700

Facsimile: (212) 930-9725

                 May 4, 2012

Synergy Pharmaceuticals Inc.

420 Lexington Avenue

Suite 1609

New York, New York 10170

Re: Synergy Pharmaceuticals Inc.’s Registration Statement on Form S-3

Ladies and Gentlemen:

We have acted as special counsel for Synergy Pharmaceuticals Inc., a Delaware corporation (the “Company”), in connection with the preparation and filing of a Registration Statement on Form S-3, (File No. 333-163316) (the “Registration Statement”) with the Securities and Exchange Commission (the “Commission”) under the Securities Act of 1933, as amended (the “Securities Act”), and the rules and regulations promulgated thereunder, and declared effective by the Commission on December 10, 2009 (the “Original Registration Statement”), as amended by Post-Effective Amendment No.1 thereto which was declared effective on May 2, 2012 (the “Post-Effective Amendment”), the Registration Statement on Form S-3 (Registration No. 333-181136) filed and effective with the Commission pursuant to Rule 462(b) under the Securities Act on May 4, 2012, (the “462(b) Registration Statement” and together with the Original Registration Statement and the Post-Effective Amendment, the “Registration Statement”), the prospectus included therein (the “Prospectus”), the preliminary prospectus supplement, dated May 3, 2012 (the “Preliminary Prospectus Supplement”) and the final prospectus supplement, dated May 4, 2012 (the “Final Prospectus Supplement” and together with the Preliminary Prospectus Supplement, the “Prospectus Supplement”), filed with the Commission pursuant to Rule 424(b) of the rules and regulations of the Securities Act.

The Prospectus Supplement pertains to an underwritten offering (the “Offering”) pursuant to the Underwriting Agreement dated May 3, 2012 between the Company and the underwriters named therein (the “Underwriting Agreement”) and relates to the issuance and sale of 10,000,000 shares of common stock, par value $0.0001 per share (“Common Stock”) of the Company (the “Firm Stock”), plus an additional 1,500,000 shares (the “Additional Shares”) of Common Stock that may be sold pursuant to the exercise of an over-allotment option (the Firm Shares and the Additional Shares are referred to herein collectively as the “Shares”).

We understand that the Shares are to be sold, as described in the Registration Statement, the Prospectus and the Prospectus Supplement, pursuant to the Underwriting Agreement filed as Exhibit 1.1 to the Current Report on Form 8-K to which this opinion is attached as Exhibit 5.1.

As such counsel and for purposes of our opinion set forth herein, we have examined and relied upon originals or copies, certified or otherwise identified to our satisfaction, of such documents, resolutions, certificates and instruments of the Company, certificates of public officials and such other instruments and documents as we have deemed necessary or appropriate as a basis for the opinion set forth herein, including, without limitation: (i) the Registration Statement; (ii) the Prospectus; (iii) the Prospectus Supplement; (iv) the Company’s Second Amended and Restated Certificate of Incorporation; and (v) the Company’s Amended and Restated Bylaws.

In our examination of the foregoing and in rendering the opinion set forth herein, we have assumed, without independent investigation or verification: (i) the genuineness of all signatures on all agreements, instruments, corporate records, certificates and other documents submitted to us; (ii) the authenticity and completeness of all agreements, instruments, corporate records, certificates and other documents submitted to us as

originals; (iii) that all agreements, instruments, corporate records, certificates and other documents submitted to us as certified, electronic, facsimile, conformed, photostatic or other copies conform to authentic originals thereof, and that such originals are authentic and complete; (iv) the legal capacity and authority of all persons or entities executing all agreements, instruments, corporate records, certificates and other documents submitted to us; (v) the due authorization, execution and delivery of all agreements, instruments, certificates and other documents by all parties thereto; (vi) that the statements contained in the certificates and comparable documents of public officials, officers and representatives of the Company and other persons on which we have relied for the purposes of this opinion letter are true and correct; and (vii) that the officers and directors of the Company have properly exercised their fiduciary duties. As to all questions of fact material to the opinion set forth herein and as to the materiality of any fact or other matter referred to herein, we have relied (without independent investigation) upon representations and certificates or comparable documents of officers and representatives of the Company.

Based upon the foregoing, and in reliance thereon, and subject to the limitations, qualifications and exceptions set forth herein, we are of the opinion that (i) the Shares have been duly authorized by all necessary corporate action on the part of the Company, and (ii) when issued and paid for in the manner described in the Registration Statement, Prospectus and Prospectus Supplement and in accordance with the terms  and conditions of the Underwriting Agreement, the Shares included therein will be validly issued, fully paid and nonassessable.

Without limiting any of the other limitations, exceptions and qualifications stated elsewhere herein, we express no opinion with regard to the applicability or effect of the laws of any jurisdiction other than the Delaware General Corporation Law (based solely upon our review of a standard compilation thereof) as in effect as of the date hereof. This opinion letter deals only with the specified legal issues expressly addressed herein, and you should not infer any opinion that is not explicitly stated herein from any matter addressed in this opinion letter.

We hereby consent to the inclusion of this opinion as an exhibit to the Registration Statement and to the references to our firm therein and in the Prospectus and the Prospectus Supplement under the caption “Legal Matters.”  In giving our consent, we do not admit that we are in the category of persons whose consent is required under Section 7 of the Securities Act or the rules and regulations thereunder.  This opinion letter speaks as of the date hereof and we assume no obligation to advise you or any other person with regard to any change in the circumstances or the law that may bear on the matters set forth herein after the date hereof, even though the change may affect the legal analysis, a legal conclusion or other matters in this opinion letter.