Cesium fluoride → (R)-1-(3-methoxy-4-(oxiran-2-ylmethoxy)phenyl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

HRID 1044415Notes

Reaction equation

HRID 1044415 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)=[CH:10][C:9]2=[O:24])=[CH:4][C:3]=1[O:25][CH3:26].[F-].[Cs+].[N+](C1C=C(S(O[CH2:42][C@H:43]2[CH2:45][O:44]2)(=O)=O)C=CC=1)([O-])=O>CN(C=O)C.C(Cl)Cl>[CH3:26][O:25][C:3]1[CH:4]=[C:5]([N:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:21])([F:22])[F:23])=[CH:16][CH:15]=3)=[CH:10][C:9]2=[O:24])[CH:6]=[CH:7][C:2]=1[O:1][CH2:42][C@H:43]1[CH2:45][O:44]1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 146513Benzenesulfonic acid, 3-nitro-, (2R)-2-oxiranylmethyl esterHCID 671350841-(4-hydroxy-3-methoxyphenyl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

Product 1

HCID 86660698(R)-1-(3-methoxy-4-(oxiran-2-ylmethoxy)phenyl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-oneYield 73.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-(4-hydroxy-3-methoxyphenyl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one Part B of Procedure 14 (38 mg, 0.105 mmol) and cesium fluoride (48 mg, 0.32 mmol) in DMF (1 mL) was stirred at RT for 30 min. Then, (R)-oxiran-2-ylmethyl 3-nitrobenzenesulfonate (35 mg, 0.13 mmol) was added and stirred overnight at RT. Diluted with DCM, washed with water, sat. NaHCO3, dried (Na2SO4), and concentrated. The crude was purified using ISCO flash chromatography (silica gel/hexanes/ethyl acetate 100:0 to 0:100 gradient) to afford the desired product (R)-1-(3-methoxy-4-(oxiran-2-ylmethoxy)phenyl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one 15A (32.1 mg, 0.08 mmol, 73.1% yield) as a light yellow solid. LC/MS 418 (M+H)+, tR 0.93 min (method 5).

Workup

  1. stirringstirred overnight at RT
  2. washwashed with water, sat. NaHCO3
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe crude was purified

Sources & evidence

ORD record
ord-1cfbb85858284c9283cce7901be4540f
Source dataset
uspto-grants-2013_10
Patent number
US08563583B2

Reaction notes

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