(+/-)-(2S,3R)-1-tert-Butoxycarbonyl-3-(tert-butyldimethylsilanyloxy)pipecolic acid methyl ester → (+/-)-(2S,3R)-1-tert-Butoxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-hydroxymethylpiperidine

HRID 501645Notes

Reaction equation

HRID 501645 reaction equation
C[O:2][C:3](=O)[C@@H:4]1[C@H:9]([O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])[CH2:8][CH2:7][CH2:6][N:5]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>C1COCC1>[C:21]([O:20][C:18]([N:5]1[CH2:6][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:4]1[CH2:3][OH:2])=[O:19])([CH3:24])([CH3:23])[CH3:22]

Participants

3

Reactant 1

HCID 68458695(+/-)-(2S,3R)-1-tert-Butoxycarbonyl-3-(tert-butyldimethylsilanyloxy)pipecolic acid methyl ester

Product 1

HCID 68457794(+/-)-(2S,3R)-1-tert-Butoxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-hydroxymethylpiperidineYield 102.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 77D (1.0 g, 2.7 mmol) in THF (10 mL) at −78° C. was added a solution of LiEt3BH (1.0 M in THF, 13.5 mL, 13.5 mmol, 5 equiv). The mixture was warmed to rt and stirred at rt for 4 h. The mixture was poured over ice and stirred vigorously for 15 min. The mixture was extracted with EtOAc (2×50 mL). The combined organic layers were washed with 0.5 N HCl (20 mL), saturated sodium bicarbonate solution (20 mL), brine (20 mL), dried (MgSO4) and evaporated to give the crude product as a colorless oil. Purification of the crude product by flash chromatography (5-50% EtOAc/hexane) gave the desired product 77E (960 mg): Rf (50% EtOAc/hexane) 0.64; HPLC (Phenomenex Luna 5 u C18 4.6×50 mm, linear gradient over 4 min) retention time 4.1 min (100%); MS (ES) m/z 346.1 [M+1]+; HRMS calcd for C17H36NO4Si 346.2414, Found 346.2419.

Workup

  1. additionThe mixture was poured over ice
  2. stirringstirred vigorously for 15 min
  3. extractionThe mixture was extracted with EtOAc (2×50 mL)
  4. washThe combined organic layers were washed with 0.5 N HCl (20 mL), saturated sodium bicarbonate solution (20 mL), brine (20 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customto give the crude product as a colorless oil
  8. customPurification of the crude product by flash chromatography (5-50% EtOAc/hexane)

Sources & evidence

ORD record
ord-508855a0bf8c44af95b33703c517625d
Source dataset
uspto-grants-2010_08
Patent number
US07772267B2

Reaction notes

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