Methanol → HCID 70035325, compound

HRID 431828Notes

Reaction equation

HRID 431828 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:12][C@H:11]([S:13][C:14]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:10][C@H:9]2[CH2:33][O:34][CH2:35][C:36]2[CH:41]=[C:40]([F:42])[C:39](F)=[CH:38][C:37]=2[F:44])[CH:5]=[CH:4][N:3]=1.[CH3:45][OH:46].[H-].[Na+].CN([CH:52]=[O:53])C>>[F:44][C:37]1[CH:38]=[C:39]([O:53][CH3:52])[C:40]([F:42])=[CH:41][C:36]=1[CH2:35][O:34][CH2:33][C@@H:9]1[CH2:10][C@@H:11]([S:13][C:14]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:12][N:8]1[C:6]1[CH:5]=[CH:4][N:3]=[C:2]([O:46][CH3:45])[N:7]=1

Participants

5

Reactant 4

HCID 887MethanolHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 86585172HCID 86585172, compound

Product 1

HCID 70035325HCID 70035325, compoundYield 54%

Procedure

A solution of 0.24 (0.4 mmol) (2S,4R)-2-Chloro-4-[2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidin-1-yl]-pyrimidine in 8 ml DMF was treated at 0° C. with 0.05 ml (1.2 mmol) MeOH and 0.054 g (1.24 mmol) 55% NaH. The reaction was kept at this temperature (6 h) and warmed up over night to RT. After extraction with aqueous saturated NH4Cl/Et2O (3×), the organic phases were washed with aq. 10% NaCl, dried (Na2SO4) and evaporated. Flash chromatography (CH2Cl2 EtOAc 95:5) gave 0.14 g (54%) (2S,4R)-4-[2-(2,5-Difluoro-4-methoxy-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidin-1-yl]-2-methoxy-pyrimidine, MS: 640 (MH+). TFA/triisopropylsilane deprotection, (see General method for S-deprotection, Method D) gave (3R,5S)-5-(2,5-Difluoro-4-methoxy-benzyloxymethyl)-1-(2-methoxy-pyrimidin-4-yl)-pyrrolidine-3-thiol, MS: 398 (MH+).

Workup

  1. customwas kept at this temperature (6 h)
  2. extractionAfter extraction with aqueous saturated NH4Cl/Et2O (3×)
  3. washthe organic phases were washed with aq. 10% NaCl
  4. dry with materialdried (Na2SO4)
  5. customevaporated

Sources & evidence

ORD record
ord-789b58e45af94199ab4cce7c9428800e
Source dataset
uspto-grants-2003_12
Patent number
US06660738B2

Reaction notes

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