Water → benzyl (2RS,3SR)-3-hydroxy-2,4,4-trimethylpyrrolidine-1-carboxylate

HRID 906977Notes

Reaction equation

HRID 906977 reaction equation
[Si]([O:8][CH:9]([C:23]([CH3:27])([CH3:26])[CH2:24]O)[CH:10]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:11])(C(C)(C)C)(C)C.C(N(CC)CC)C.S(Cl)(C)(=O)=O.O>C1COCC1>[OH:8][CH:9]1[C:23]([CH3:24])([CH3:26])[CH2:27][N:12]([C:13]([O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[O:22])[CH:10]1[CH3:11]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59273056Benzyl [2-(tert-butyldimethylsilyloxy)-4-hydroxy-1,3,3-trimethylbutyl]carbamate

Product 1

HCID 67390300benzyl (2RS,3SR)-3-hydroxy-2,4,4-trimethylpyrrolidine-1-carboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution (20 mL) of benzyl [2-(tert-butyldimethylsilyloxy)-4-hydroxy-1,3,3-trimethylbutyl]carbamate (1.38 g) and triethylamine (0.73 mL) in THF was added mesyl chloride (0.352 mL) at 0° C., and the mixture was stirred at 0° C. for 45 min. The reaction mixture was added to water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. To a solution (20 mL) of the residue in THF was added 1M potassium tert-butoxide—THF solution (3.8 mL). After stirring at room temperature for 1 hr, water was added and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. To a solution (10 mL) of the residue in THF was added 1M tetrabutylammonium fluoride—THF solution (4 mL), and the mixture was stirred at room temperature for 17 hr. The reaction mixture was added to water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=50/1→1/2) to give the title compound as a colorless solid (yield: 842 mg, yield: 92%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. additionTo a solution (20 mL) of the residue in THF was added 1M potassium tert-butoxide—THF solution (3.8 mL)
  6. stirringAfter stirring at room temperature for 1 hr
  7. additionwater was added
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe extract was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. additionTo a solution (10 mL) of the residue in THF was added 1M tetrabutylammonium fluoride—THF solution (4 mL)
  13. stirringthe mixture was stirred at room temperature for 17 hr
  14. additionThe reaction mixture was added to water
  15. extractionthe mixture was extracted with ethyl acetate
  16. washThe extract was washed with saturated brine
  17. dry with materialdried over anhydrous magnesium sulfate
  18. concentrationconcentrated under reduced pressure
  19. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=50/1→1/2)

Sources & evidence

ORD record
ord-74688b5e93f146f597826dcbeaa9da7d
Source dataset
uspto-grants-2011_09
Patent number
US08013008B2

Reaction notes

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