Dichloromethane ethylacetate → (2S,4R)-[1-(naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidin-2-yl]-methanol

HRID 458304Notes

Reaction equation

HRID 458304 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].C[O:8][C:9]([C@@H:11]1[CH2:15][C@@H:14]([S:16][C:17]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)([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)[CH2:13][N:12]1[S:36]([C:39]1[CH:48]=[CH:47][C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:40]=1)(=[O:38])=[O:37])=O.C(Cl)Cl.CCOC(C)=O>C1COCC1>[CH:40]1[C:41]2[C:46](=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH:47]=[CH:48][C:39]=1[S:36]([N:12]1[CH2:13][C@H:14]([S:16][C:17]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:15][C@H:11]1[CH2:9][OH:8])(=[O:38])=[O:37]

Participants

5

Reactant 3

HCID 21226138Dichloromethane ethylacetate2×HCID 21226445Aluminium lithium hydrideHCID 69435513(2S,4R)-1-(naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid methyl ester

Product 1

HCID 69431241(2S,4R)-[1-(naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidin-2-yl]-methanolYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Ester reduction, Method A: 57 ml (57 mmol, 1M THF solution) of LAH was added during 15 min to a cold solution (−20° C.) of 28.2 g (47.5 mmol, ca. (2S,4R)/(2R,4R)-isomer ca 4:1) (2S,4R)-1-(naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid methyl ester in 460 ml THF. The reaction was stirred for 20 min, cooled to −78° C. and quenched with a suspension of 15 g silica gel/15 g MgSO4 7H2O in 60 ml aqueous 10% KHSO4. The suspension was stirred for 15 min at room temperature, filtered and washed with THF. After evaporation of the THF, the residue was taken up in CH2Cl2, dried over Na2SO4 and evaporated to give 29.2 g crude product. Flash column chromatography on silica gel with CH2Cl2/EtOAc(2.5%) to CH2Cl2/EtOAc(10%) gave 21.7 g (81%) of (2S,4R)-[1-(naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidin-2-yl]-methanol and 1.0 g (4%) of [(2R,4R)-4-mercapto-1-(naphthalene-2-sulfonyl)-pyrrolidin-2-yl]MS: 566 (MH+).

Workup

  1. customquenched with a suspension of 15 g silica gel/15 g MgSO4 7H2O in 60 ml aqueous 10% KHSO4
  2. stirringThe suspension was stirred for 15 min at room temperature
  3. filtrationfiltered
  4. washwashed with THF
  5. customAfter evaporation of the THF
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customto give 29.2 g crude product

Sources & evidence

ORD record
ord-89b7a4e99ffe4eab8a528aa5af9b19ad
Source dataset
uspto-grants-2007_03
Patent number
US07189756B2

Reaction notes

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