2-Methoxyethanol → 4-{(S)-3-[2-Chloro-4-(2-methoxy-ethoxy)-benzenesulfonyl]-pyrrolidin-1-yl}-2-methylsulfanyl-6-trifluoromethyl-pyrimidine

HRID 38045Notes

Reaction equation

HRID 38045 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](F)[CH:5]=[CH:4][C:3]=1[S:9]([C@H:12]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[N:20]=[C:19]([S:27][CH3:28])[N:18]=2)[CH2:13]1)(=[O:11])=[O:10].C([O-])([O-])=O.[Cs+].[Cs+].[CH3:35][O:36][CH2:37][CH2:38][OH:39]>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([O:39][CH2:38][CH2:37][O:36][CH3:35])[CH:5]=[CH:4][C:3]=1[S:9]([C@H:12]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[C:21]([C:23]([F:25])([F:24])[F:26])[N:20]=[C:19]([S:27][CH3:28])[N:18]=2)[CH2:13]1)(=[O:11])=[O:10]

Participants

6

Reactant 3

HCID 80192-MethoxyethanolHCID 10796Cesium carbonateHCID 67495600HCID 67495600, compound

Product 1

HCID 674952814-{(S)-3-[2-Chloro-4-(2-methoxy-ethoxy)-benzenesulfonyl]-pyrrolidin-1-yl}-2-methylsulfanyl-6-trifluoromethyl-pyrimidine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

4-[(S)-3-(2-Chloro-4-fluoro-benzenesulfonyl)-pyrrolidin-1-yl]-2-methylsulfanyl-6-trifluoromethyl-pyrimidine (Intermediate of example 42; 300 mg) was dissolved in DMF (5.0 mL). Cs2CO3 (429 mg) and 2-methoxy-ethanol (0.10 mL) were added. The reaction mixture was stirred for 24 h at 25° C. After that, the reaction mixture was diluted with ethyl acetate (20 mL) and extracted with water (10 mL). The organic layers were dried over Na2SO4, filtrated and evaporated to dryness. The crude material was purified by flash chromatography (50 g silica gel; ethyl acetate/n-heptane) to yield a colorless waxy solid (170 mg; 50%) MS: m/z=512.2 [M+H]+.

Workup

  1. extractionextracted with water (10 mL)
  2. dry with materialThe organic layers were dried over Na2SO4
  3. filtrationfiltrated
  4. customevaporated to dryness
  5. customThe crude material was purified by flash chromatography (50 g silica gel; ethyl acetate/n-heptane)
  6. customto yield a colorless waxy solid (170 mg; 50%)

Sources & evidence

ORD record
ord-f7f5d255699140679fec3e26f53bcc10
Source dataset
uspto-grants-2013_09
Patent number
US08524710B2

Reaction notes

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