Methanol → (3S*,4S*)-4-hydroxymethyl-pyrrolidine-1,3-dicarboxylic acid 1-tert-butylester 3-ethyl ester

HRID 1158324Notes

Reaction equation

HRID 1158324 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[C@H:10]([C:11](O)=[O:12])[CH2:9][N:8]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:7]1)=[O:5])[CH3:2].CSC.B.CO>C1COCC1>[CH2:1]([O:3][C:4]([C@H:6]1[C@H:10]([CH2:11][OH:12])[CH2:9][N:8]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:7]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 11437663trans-1-Boc-3,4-pyrrolidinedicarboxylic acid, 3-ethyl esterHCID 12423031(Dimethyl sulfide)trihydroboron

Product 1

HCID 59512291(3S*,4S*)-4-hydroxymethyl-pyrrolidine-1,3-dicarboxylic acid 1-tert-butylester 3-ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of (3S*,4S*)-pyrrolidine-1,3,4-tricarboxylic acid 1-tert-butyl ester 3-ethyl ester (10 g, 34.8 mmol) in THF (180 mL), a solution of borane dimethylsulfide complex (2N in THF, 24.4 mL, 48.7 mmol) is added slowly at −10° C. The mixture is stirred at −10° C. for 20 min, then allowed to reach RT and further stirred for 4 h. MeOH is carefully added (exothermic!), and the mixture is concentrated under reduced pressure. MeOH is again added, and the mixture is concentrated. This operation is repeated 3 times, then the mixture is finally taken up into a saturated aqueous solution of NaHCO3 and extracted 3 times with CH2Cl2. The combined organic extracts are dried over Na2SO4, filtered and concentrated. The crude material is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH from 100:0 to 95:5) to give the title compound as product. TLC, Rf (AcOEt)=0.52. MS (LC-MS): 174.1 [M+H-Boc]+.

Workup

  1. customto reach RT
  2. stirringfurther stirred for 4 h
  3. concentrationthe mixture is concentrated under reduced pressure
  4. additionMeOH is again added
  5. concentrationthe mixture is concentrated
  6. extractionextracted 3 times with CH2Cl2
  7. dry with materialThe combined organic extracts are dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH from 100:0 to 95:5)

Sources & evidence

ORD record
ord-602776c2c24a4095b7b5a7ab90593da6
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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