Pyridine → (S)-N-((R)-1-(4-fluoro-3-(vinyloxy)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide

HRID 1874306Notes

Reaction equation

HRID 1874306 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]([NH:30][S@:31]([C:33]([CH3:36])([CH3:35])[CH3:34])=[O:32])([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][C:3]=1[OH:37].N1C=CC=[CH:40][CH:39]=1.C(B1OB(C=C)OB(C=C)O1)=C>C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Cu+2]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]([NH:30][S@:31]([C:33]([CH3:34])([CH3:36])[CH3:35])=[O:32])([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:27])([F:28])[CH:24]([F:25])[F:26])[CH:19]=[C:18]([F:29])[CH:17]=2)[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:4][C:3]=1[O:37][CH:39]=[CH2:40]

Participants

6

Reactant 3

HCID 1049PyridineHCID 2734807TrivinylboroxinHCID 59458952(S)-N-((R)-1-(4-fluoro-3-hydroxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide

Product 1

HCID 59458450(S)-N-((R)-1-(4-fluoro-3-(vinyloxy)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamideYield 87%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)—N—((R)-1-(4-fluoro-3-hydroxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide prepared as described in Procedure 3, 4, 5, 6 and 59 (0.545 g, 1 mmol) in CH2Cl2 (10 mL) was added Cu(OAc)2 (0.182 g, 1 mmol), followed by pyridine (0.79 g, 10 mmol) and 2,4,6-trivinyl-1,3,5,2,4,6-trioxatriborinane (0.159 g, 0.66 mmol). The reaction mixture was stirred overnight under ambient air and filtered through a plug of celite and neutral alumina. The solid was washed with ethyl acetate and the filtrate was concentrated under reduced pressure to yield (S)—N—((R)-1-(4-fluoro-3-(vinyloxy)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide as an off-white foam (0.495 g, 87% yield). LCMS: RT=3.653 min [M+H] 572.2 (Phenomenex Luna C18 5μ column, eluting with 10-90% aqueous acetonitrile containing 0.1% trifluoroacetic acid over a 4 minute gradient, monitoring at 220 nM). 1H NMR (CDCl3) ppm 7.2-7.1 (m, 5H), 7.02 (d, J=6.2 Hz, 1 H), 6.89 (d, J=6.2 Hz, 2H), 6.82 (d, J=8.8 Hz, 1H), 6.68 (br, 2H), 6.54 (dd, J=6.2 Hz, 13.6 Hz, 1H), 5.84 (t, J=52.7 Hz, 1H), 4.62 (dd, J=2.2 Hz, 13.6 Hz, 1H), 4.40 (dd, J=2.2 Hz, 5.7 Hz, 1H), 4.21 (s, 1H), 3.95 (d, J=12.8 Hz, 1H), 3.55 (d, J=12.7 Hz, 1H), 1.19 (s, 9H).

Workup

  1. filtrationfiltered through a plug of celite and neutral alumina
  2. washThe solid was washed with ethyl acetate
  3. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-6e29145745544465869b345e0f1c38e3
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

Loading…