Ethanethiol → (S)-1-(4-(3-(ethylthio)-2-hydroxypropoxy)-3-methoxyphenyl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

HRID 1044416Notes

Reaction equation

HRID 1044416 reaction equation
[CH2:1]([SH:3])[CH3:2].[OH-].[K+].[CH3:6][O:7][C:8]1[CH:9]=[C:10]([N:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=3)=[CH:21][C:20]2=[O:35])[CH:11]=[CH:12][C:13]=1[O:14][CH2:15][C@H:16]1[CH2:18][O:17]1>C1COCC1.CCOC(C)=O>[CH2:1]([S:3][CH2:18][C@@H:16]([OH:17])[CH2:15][O:14][C:13]1[CH:12]=[CH:11][C:10]([N:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][C:28]([C:31]([F:33])([F:34])[F:32])=[CH:27][CH:26]=3)=[CH:21][C:20]2=[O:35])=[CH:9][C:8]=1[O:7][CH3:6])[CH3:2]

Participants

6

Reactant 3

HCID 6343EthanethiolHCID 14797Potassium HydroxideHCID 86660698(R)-1-(3-methoxy-4-(oxiran-2-ylmethoxy)phenyl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

Product 1

HCID 67134772(S)-1-(4-(3-(ethylthio)-2-hydroxypropoxy)-3-methoxyphenyl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-oneYield 76%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethanethiol (47.6 mg, 0.76 mmol) and 25% aq. potassium hydroxide (172 mg, 0.77 mmol) were added to a solution of (R)-1-(3-methoxy-4-(oxiran-2-ylmethoxy)phenyl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one (32 mg, 0.08 mmol) Part A in THF (1.5 mL). The mixture was stirred overnight at RT. Diluted with EtOAc, washed with sat. NaHCO3, dried (Na2SO4), and concentrated. The residue was purified using ISCO flash chromatography (silica gel/hexanes/ethyl acetate 100:0 to 0:100 gradient) to afford the desired product (S)-1-(4-(3-(ethylthio)-2-hydroxypropoxy)-3-methoxyphenyl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one 15B (28 mg, 0.06 mmol, 76% yield) as a light yellow solid. LC/MS 480 (M+H)+, tR 0.97 min (method 5).

Workup

  1. washwashed with sat. NaHCO3
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe residue was purified

Sources & evidence

ORD record
ord-ec159efebc7b4afa8cc85a9cd19811f6
Source dataset
uspto-grants-2013_10
Patent number
US08563583B2

Reaction notes

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