2,2,2-Trifluoroethanol → HCID 18753241, compound

HRID 1838190Notes

Reaction equation

HRID 1838190 reaction equation
[F:1][C:2]([F:6])([F:5])[CH2:3][OH:4].[H-].[Na+].Cl[C:10]1[C:15]([C:16]#[N:17])=[C:14]([N:18]2[CH2:23][CH2:22][CH:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:20][CH2:19]2)[N:13]=[C:12]([S:30][CH3:31])[N:11]=1>O1CCCC1>[CH3:31][S:30][C:12]1[N:13]=[C:14]([N:18]2[CH2:19][CH2:20][CH:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:22][CH2:23]2)[C:15]([C:16]#[N:17])=[C:10]([O:4][CH2:3][C:2]([F:6])([F:5])[F:1])[N:11]=1

Participants

5

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydrideHCID 18753228HCID 18753228, compound

Product 1

HCID 18753241HCID 18753241, compoundYield 63.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 56 mg (0.55 mmol) of 2,2,2-trifluoroethanol in 5 ml of tetrahydrofurane was cooled to 0° C. and treated under an argon atmosphere with 23 mg (0.52 mmol) of sodium hydride (55% dispersion in oil). The mixture was kept at 0° C. during 10 min, then a solution of 200 mg (0.58 mmol) of 4-chloro-2-methylsulfanyl-6-(4-phenyl-piperidin-1-yl)-pyrimidine-5-carbonitrile in 5 ml of tetrahydrofurane was added and, thereupon, the mixture was warmed to room temperature and stirring continued during 36 hours. For the working-up, the reaction mixture was evaporated and the residue obtained was directly chromatographed on silica gel using a 9:1 mixture of hexane and ethyl acetate as the eluent yielding 142 mg (0.35 mmol, 60% of theory) of the 2-methylsulfanyl-4-(4-phenyl-piperidin-1-yl)-6-(2,2,2-trifluoro-ethoxy)-pyrimidine-5-carbonitrile as an amorphous, white solid; MS: [M+H]+=409.

Workup

  1. waitcontinued during 36 hours
  2. customthe reaction mixture was evaporated
  3. customthe residue obtained
  4. customwas directly chromatographed on silica gel using
  5. additiona 9:1 mixture of hexane and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-69b643ee29fc4e239fefe5ccae076d4a
Source dataset
uspto-grants-2004_01
Patent number
US06673795B2

Reaction notes

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