trans-3-hydroxy-L-proline → 1,1-Dimethylethyl (2R,3S)-3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-2-(hydroxymethyl)-1-pyrrolidinecarboxylate

HRID 751129Notes

Reaction equation

HRID 751129 reaction equation
C[O:2][C:3]([C@@H:5]1[C@H:9]([O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])[CH2:8][CH2:7][N:6]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=O.O[C@H]1CCN[C@@H]1C(O)=O.COC(=O)[C@@H]1[C@@H](O[Si](C(C)(C)C)(C)C)CCN1C(OC(C)(C)C)=O.C([BH-](CC)CC)C.[Li+]>C1COCC1>[C:21]([O:20][C:18]([N:6]1[CH2:7][CH2:8][C@H:9]([O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])[C@H:5]1[CH2:3][OH:2])=[O:19])([CH3:24])([CH3:23])[CH3:22]

Participants

6

Reactant 4

HCID 440575trans-3-hydroxy-L-prolineHCID 23664628LithiumtriethylborohydrideHCID 58841066Methyl (2S,3S)-1-Boc-3-[(tert-butyldimethylsilyl)oxy]pyrrolidine-2-carboxylateHCID 68455583(2S,3R)-3-(tert-Butyldimethylsilanyloxy)pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Product 1

HCID 109256021,1-Dimethylethyl (2R,3S)-3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-2-(hydroxymethyl)-1-pyrrolidinecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Following procedures described for the preparation of (2S,3R)—N-tert-butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)proline methyl ester (51A), (2S,3S)-3-hydroxyproline was converted to (2S,3S)—N-tert-butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)proline methyl ester. To this material (4.3 g, 12 mmol) in THF (75 mL) at −78° C. under nitrogen was added dropwise 1.0 M lithium triethylborohydride in THF (60 mL, 60 mmol). The reaction was allowed to warm to rt and was stirred for 4 h. The reaction was quenched by pouring over ice (150 g) and stirring for 30 min. The product was extracted into EtOAc and washed with saturated aqueous NaHCO3. The organics were dried over MgSO4, filtered and concentrated. Purification by flash chromatography (silica gel, 0-15% EtOAc in hexanes) provided the title compound (3.3 g). 61B. (2S,3S)—N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-formyl-pyrrolidine

Workup

  1. customThe reaction was quenched
  2. additionby pouring over ice (150 g)
  3. stirringstirring for 30 min
  4. extractionThe product was extracted into EtOAc
  5. washwashed with saturated aqueous NaHCO3
  6. dry with materialThe organics were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by flash chromatography (silica gel, 0-15% EtOAc in hexanes)

Sources & evidence

ORD record
ord-6bfa9c412c564be2bcdfd30146a2ca09
Source dataset
uspto-grants-2008_07
Patent number
US07405234B2

Reaction notes

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