Triethylsilane → (3R,5S)-5-benzyloxymethyl-1-methanesulfonyl-pyrrolidine-3-thiol

HRID 458340Notes

Reaction equation

HRID 458340 reaction equation
[CH2:1]([O:8][CH2:9][C@@H:10]1[CH2:14][C@@H:13]([S:15]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:12][N:11]1[S:35]([CH3:38])(=[O:37])=[O:36])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([SiH](CC)CC)C>C(O)(C(F)(F)F)=O>[CH2:1]([O:8][CH2:9][C@H:10]1[N:11]([S:35]([CH3:38])(=[O:37])=[O:36])[CH2:12][C@H:13]([SH:15])[CH2:14]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 12052TriethylsilaneHCID 69429844(2S,4R)-2-benzyloxymethyl-1-methanesulfonyl-4-tritylsulfanyl-pyrrolidine

Product 1

HCID 86584848(3R,5S)-5-benzyloxymethyl-1-methanesulfonyl-pyrrolidine-3-thiolYield 75%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

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. customthe mixture was evaporated
  2. custompurified by flash-chromatography on silica gel (Hexane/EtOAc 4:1 to 1:4)

Sources & evidence

ORD record
ord-a1a37805c6e14900a358f1b99f063406
Source dataset
uspto-grants-2007_03
Patent number
US07189756B2

Reaction notes

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