2-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl → HCID 56932571, compound

Participants

Reaction Conditions

Reaction Steps

In a pressure tube (3S)-3-methyl-4-(((2S)-4-(2-thiophenylsulfonyl)-2-piperazinyl)methyl)morpholine dihydrochloride (133 mg, 0.318 mmol, Example 82, Step 2), 2-(4-bromophenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (123 mg, 0.381 mmol, Bioorg. Med. Chem. Lett. 2002, 12, 3009), Pd2(dba)3 (18.28 mg, 0.032 mmol, Strem Chemicals, Newburyport, Mass.), dicyclohexyl(2′,6′-diisopropoxybiphenyl-2-yl)phosphine (RuPhos) (14.83 mg, 0.032 mmol, Strem Chemicals, Newburyport, Mass.), and sodium tert-butoxide (122 mg, 1.272 mmol) were combined and suspended in toluene (5 mL). Nitrogen gas was bubbled through the solution for 5 min. The reaction vial was sealed and heated to 100° C. for 15 h. The reaction mixture was then diluted with water and EtOAc. The aqueous mixture was extracted with EtOAc (2×20 mL). The organic extracts were combined and dried over MgSO4, filtered, and concentrated. The crude material was purified by purified via reverse-phase preparative HPLC using a Phenomenex Gemini C18 column (30×150 mm, 10 μm) eluting with 0.1% TFA in MeCN/H2O (10% to 100% over 15 min) to afford 1,1,1,3,3,3-hexafluoro-2-(4-((2S)-2-(((3S)-3-methyl-4-morpholinyl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (23 mg).

Provenance & Evidence