Water → HCID 86602702, compound

HRID 1375039Notes

Reaction equation

HRID 1375039 reaction equation
[Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:9][O:10][C:11](=[O:42])[C:12]1[CH:17]=[CH:16][C:15]([CH2:18][C@@H:19]2[CH2:24][NH:23][CH2:22][CH2:21][N:20]2[C:25](=[O:40])[C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=2)=[CH:14][C:13]=1[OH:41].C(N(CC)CC)C.O>CN(C)C1C=CN=CC=1.ClCCl>[CH3:9][O:10][C:11](=[O:42])[C:12]1[CH:17]=[CH:16][C:15]([CH2:18][C@@H:19]2[CH2:24][NH:23][CH2:22][CH2:21][N:20]2[C:25](=[O:40])[C:26]2[CH:27]=[C:28]([C:36]([F:37])([F:38])[F:39])[CH:29]=[C:30]([C:32]([F:35])([F:33])[F:34])[CH:31]=2)=[CH:14][C:13]=1[O:41][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 8471Triethylamine2×HCID 28928tert-Butyldimethylsilyl chloride2×HCID 53763260HCID 53763260, compound

Product 1

HCID 86602702HCID 86602702, compoundYield 54.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

tert-Butyldimethylsilyl chloride (2.34 g) was added to a solution of 4-[[(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-piperazin-2-yl]methyl]-2-hydroxybenzoic acid methyl ester (2.56 g), 4-(dimethylamino)pyridine (126 mg) and triethylamine (2.51 ml) in dichloromethane (50 ml) at room temperature. After stirring at room temperature for 15 hours, additional triethylamine (2.51 ml) and tert-butyldimethylsilyl chloride (2.34 g) were added and the whole mixture was stirred for further 1 day. Water (200 ml) was added to the mixture, and the resulting mixture was extracted with dichloromethane. The organic extracts were washed with water and brine successively, dried over magnesium sulfate, and evaporated under reduced pressure to give crude oil. The oil was purified by column chromatography on silica gel using a mixed solvent of dichloromethane and methanol to give 4-[[(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]piperazin-2-yl]-methyl]-2-(tert-butyldimethylsilyloxy)benzoic acid methyl ester (1.72 g).

Workup

  1. stirringthe whole mixture was stirred for further 1 day
  2. extractionthe resulting mixture was extracted with dichloromethane
  3. washThe organic extracts were washed with water and brine successively
  4. dry with materialdried over magnesium sulfate
  5. customevaporated under reduced pressure
  6. customto give crude oil
  7. customThe oil was purified by column chromatography on silica gel using a mixed solvent of dichloromethane and methanol

Sources & evidence

ORD record
ord-d5d7797229754fbda58f66a197118fff
Source dataset
uspto-grants-2007_01
Patent number
US07166598B2

Reaction notes

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