Benzyl Bromide → (2S,4R)-2-benzyloxymethyl-1-methanesulfonyl-4-tritylsulfanyl-pyrrolidine

HRID 458339Notes

Reaction equation

HRID 458339 reaction equation
[CH3:1][S:2]([N:5]1[CH2:9][C@H:8]([S:10][C:11]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:7][C@H:6]1[CH2:30][OH:31])(=[O:4])=[O:3].[CH2:32](Br)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[H-].[Na+].C(Br)C1C=CC=CC=1.[H-].[Na+]>CN(C=O)C>[CH2:32]([O:31][CH2:30][C@@H:6]1[CH2:7][C@@H:8]([S:10][C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:9][N:5]1[S:2]([CH3:1])(=[O:3])=[O:4])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 4

HCID 7498Benzyl Bromide2×HCID 24758Sodium hydrideHCID 23668858benzylbromide NaHHCID 69433309(2S,4R)-(1-methanesulfonyl-4-tritylsulfanyl-pyrrolidin-2-yl)-methanol

Product 1

HCID 69429844(2S,4R)-2-benzyloxymethyl-1-methanesulfonyl-4-tritylsulfanyl-pyrrolidineYield 59.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

9.07 g (20 mmol) of (2S,4R)-(1-methanesulfonyl-4-tritylsulfanyl-pyrrolidin-2-yl)-methanol and 9.5 ml (80 mmol) of benzylbromide were dissolved in 660 ml DMF, cooled to 0° C. and treated with 1.4 g (32 mmol) of 55% NaH over 15 min in 4 portions. The reaction was warmed up over night and treated with 4.75 ml (40 mmol) benzylbromide/700 mg (16 mmol) 55% NaH and 6 h later again with the same amount of benzylbromide/NaH. After further 16 h at room temperature the reaction was quenched with saturated NH4Cl solution/EtOAc (3x). The organic phase was washed with aqueous 10% NaCl solution, dried over Na2SO4 and evaporated to give 25 g crude product. Flash-chromatography on silica gel (Hexane/EtOAc 4:1 to 1:4) gave 6.43 g (59%) of (2S,4R)-2-benzyloxymethyl-1-methanesulfonyl-4-tritylsulfanyl-pyrrolidine, MS: 544 (MH+). 6.4 g (11.77 mmol) (2S,4R)-2-benzyloxymethyl-1-methanesulfonyl-4-tritylsulfanyl-pyrrolidine were dissolved in 170 ml TFA and treated at 0° C. with 18.75 ml (117.7 mmol) of triethylsilane. After 18 h at 0° C., the mixture was evaporated and purified by flash-chromatography on silica gel (Hexane/EtOAc 4:1 to 1:4) to give 2.66 g (72%) of (3R,5S)-5-benzyloxymethyl-1-methanesulfonyl-pyrrolidine-3-thiol, MS: 302 (MH+).

Workup

  1. temperatureThe reaction was warmed up over night
  2. customAfter further 16 h at room temperature the reaction was quenched with saturated NH4Cl solution/EtOAc (3x)
  3. washThe organic phase was washed with aqueous 10% NaCl solution
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customto give 25 g crude product

Sources & evidence

ORD record
ord-a78e6d8981e44cf2ae26a4824c17b706
Source dataset
uspto-grants-2007_03
Patent number
US07189756B2

Reaction notes

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