Sodium hydride → (2S,4R)-2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 431822Notes

Reaction equation

HRID 431822 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([S:13][C:14]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][C@H:9]1[CH2:33][OH:34])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:35][C:36]1[CH:43]=[C:42]([F:44])[C:41]([F:45])=[CH:40][C:37]=1[CH2:38]Br.[H-].[Na+].[NH4+].[Cl-]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([S:13][C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:10][C@H:9]1[CH2:33][O:34][CH2:38][C:37]1[CH:40]=[C:41]([F:45])[C:42]([F:44])=[CH:43][C:36]=1[F:35])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 27770572,4,5-Trifluorobenzyl BromideHCID 11271474(2S,4R)-2-hydroxymethyl-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 11786887(2S,4R)-2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid tert-butyl esterYield 46.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 15.5 g (32.59 mmol) (2S,4R)-2-Hydroxymethyl-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid tert-butyl ester and 24.7 g (109.77 mmol) 2,4,5-trifluoro-benzylbromide in 700 ml DMF at 0° C. was treated with 2.28 g (52.14 mmol) of 55% NaH in 4 portions and warmed up to RT during 7 h. The reaction was cooled to 0° C. and treated with 500 ml aqueous saturated NH4Cl solution, extracted with EtOAc (3×). The organic phase was washed with 10% NaCl dried over Na2SO4 and evaporated. Flash column chromatography on silica gel with hexane/EtOAc (9:1 to 8.5:1.5) gave 9.37 g (46%) of (2S,4R)-2-(2,4,5-Trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid tert-butyl ester, MS: 620 (MH+).

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. extractionextracted with EtOAc (3×)
  3. washThe organic phase was washed with 10% NaCl
  4. dry with materialdried over Na2SO4
  5. customevaporated

Sources & evidence

ORD record
ord-39065d201d054f71a56e22b30c240a31
Source dataset
uspto-grants-2003_12
Patent number
US06660738B2

Reaction notes

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