Water → Benzyl (2s)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-methylpiperidine-1-carboxylate

HRID 2046661Notes

Reaction equation

HRID 2046661 reaction equation
[CH2:1]([O:8][C:9](=[O:26])[NH:10][C@@H:11]([CH3:25])[CH:12]([O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[CH2:13][CH2:14][CH2:15]O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.O>O1CCCC1>[Si:18]([O:17][CH:12]1[CH2:13][CH2:14][CH2:15][N:10]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:26])[C@H:11]1[CH3:25])([C:21]([CH3:23])([CH3:22])[CH3:24])([CH3:19])[CH3:20]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59370508benzyl((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxy-1-methylpentyl)carbamate

Product 1

HCID 59370543Benzyl (2s)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-methylpiperidine-1-carboxylateYield 63.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution (15 mL) of benzyl((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxy-1-methylpentyl)carbamate (430 mg) in tetrahydrofuran were added triethylamine (0.235 mL) and methanesulfonyl chloride (0.105 mL) under ice-cooling, and the mixture was stirred at room temperature for 30 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (20 mL). Potassium tert-butoxide (152 mg) was added under ice-cooling, and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with 0.1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate=9:1→2:1) to give the title compound (yield: 260 mg) as a colorless oil.

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in tetrahydrofuran (20 mL)
  7. additionPotassium tert-butoxide (152 mg) was added under ice-
  8. temperaturecooling
  9. stirringthe mixture was stirred at room temperature for 1 hr
  10. additionWater was added to the reaction mixture
  11. extractionthe mixture was extracted with ethyl acetate
  12. washThe extract was washed with 0.1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine
  13. dry with materialdried over anhydrous sodium sulfate
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate=9:1→2:1)

Sources & evidence

ORD record
ord-f971024d6f82437694afd453d98356cd
Source dataset
uspto-grants-2013_11
Patent number
US08592452B2

Reaction notes

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