Dicyclohexylcarbodiimide → (RS)-1-ethynyl-1-(3-phenoxyphenyl)methyl (RS)-2-[2-(2-methylprop-2-yl)-pyrimidin-5-yl]-3-methylbutyrate

HRID 34599

Reaction equation

HRID 34599 reaction equation
C1(N=C=NC2CCCCC2)CCCCC1.[CH3:16][C:17]([C:20]1[N:25]=[CH:24][C:23]([CH:26]([CH:30]([CH3:32])[CH3:31])[C:27]([OH:29])=[O:28])=[CH:22][N:21]=1)([CH3:19])[CH3:18].[C:33]([CH:35](O)[C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([O:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:37]=1)#[CH:34]>ClCCl.CN(C)C1C=CN=CC=1>[CH3:19][C:17]([C:20]1[N:21]=[CH:22][C:23]([CH:26]([CH:30]([CH3:32])[CH3:31])[C:27]([O:29][CH:35]([C:33]#[CH:34])[C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([O:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[CH:37]=2)=[O:28])=[CH:24][N:25]=1)([CH3:16])[CH3:18]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 129190923-Phenoxy-alpha-ethynylbenzylalcoholHCID 13911492(RS)-2-[2-(2-methylprop-2-yl)pyrimidin-5-yl]-3-methylbutyric acid

Product 1

HCID 13911493(RS)-1-ethynyl-1-(3-phenoxyphenyl)methyl (RS)-2-[2-(2-methylprop-2-yl)-pyrimidin-5-yl]-3-methylbutyrateYield 90.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A solution of N,N'-dicyclohexylcarbodiimide (0.2 g) in dichloromethane (5 cm3) was added to a stirred mixture of (RS)-2-[2-(2-methylprop-2-yl)pyrimidin-5-yl]-3-methylbutyric acid (0.26 g), (RS)-α-ethynyl-3-phenoxybenzyl alcohol (0.224 g), 4-dimethylaminopyridine (0.02 g) and dry dichloromethane (5 cm3) and the resultant mixture stirred for 2 hours. The precipitate which formed was removed by filtration and the filtrate concentrated by evaporation of the solvent under reduced pressure. The residual oil was purified by column chromatography using a silica column eluted with a mixture of ethyl acetate (1 part by volume) and petroleum ether (boiling range 60° to 80° C., 1 part by volume) to yield (RS)-1-ethynyl-1-(3-phenoxyphenyl)methyl (RS)-2-[2-(2-methylprop-2-yl)-pyrimidin-5-yl]-3-methylbutyrate (0.4g), as a mixture of diastereoisomers.

Workup

  1. customThe precipitate which formed
  2. customwas removed by filtration
  3. concentrationthe filtrate concentrated by evaporation of the solvent under reduced pressure
  4. customThe residual oil was purified by column chromatography
  5. washeluted with a mixture of ethyl acetate (1 part by volume) and petroleum ether (boiling range 60° to 80° C., 1 part by volume)

Sources & evidence

ORD record
ord-c386507b28164d92ae62632ecf157c70
Source dataset
uspto-grants-1988_08
Patent number
US04762835

Linked notes

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