tert-Butyl-(2S,3R)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-formylpyrrolidine-1-carboxylate → (2R,3R)-3-(tert-Butyl-dimethylsilanyloxy)-2-[(1S)-(1-hydroxy-2-methylpropyl)]pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1864712Notes

Reaction equation

HRID 1864712 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[CH:21]=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:23]([Mg]Cl)([CH3:25])[CH3:24]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[C@@H:21]([OH:22])[CH:23]([CH3:25])[CH3:24])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 16732142tert-Butyl-(2S,3R)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-formylpyrrolidine-1-carboxylateHCID 178418918HCID 178418918, compound

Product 1

HCID 68459442(2R,3R)-3-(tert-Butyl-dimethylsilanyloxy)-2-[(1S)-(1-hydroxy-2-methylpropyl)]pyrrolidine-1-carboxylic acid tert-butyl esterYield 79.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

To (2S,3R)-3-(tert-butyldimethylsilanyloxy)-2-formylpyrrolidine-1-carboxylic acid tert-butyl ester (7C) (6.50 g, 19.8 mmol) in THF (100 mL) at −78° C. was added a 2M THF solution of isopropylmagnesium chloride (30.0 mL, 60.0 mmol) over 20 min. The cold bath was removed and the reaction was stirred for 1 h. The reaction was then cooled to 60° C. and was quenched with saturated aqueous ammonium chloride. After warming to rt, the whole was diluted with EtOAc. The layers were separated and the organic layer washed with water and brine, then dried (MgSO4), filtered and concentrated. The resulting residue was purified via flash chromatography eluting with 20% EtOAc/hexane to provide (2R,3R)-3-(tert-butyldimethylsilanyloxy)-2-[(1S)-(1-hydroxy-2-methyl-propyl)]-pyrrolidine-1-carboxylic acid tert-butyl ester (10A) (5.90 g).

Workup

  1. customThe cold bath was removed
  2. customwas quenched with saturated aqueous ammonium chloride
  3. temperatureAfter warming to rt
  4. additionthe whole was diluted with EtOAc
  5. customThe layers were separated
  6. washthe organic layer washed with water and brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified via flash chromatography
  11. washeluting with 20% EtOAc/hexane

Sources & evidence

ORD record
ord-89447720567f4becadd61ccba4a7b2ec
Source dataset
uspto-grants-2009_12
Patent number
US07625923B2

Reaction notes

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