Ammonium Chloride → Benzyl 4-hydroxy-4-methylpiperidine-1-carboxylate

HRID 390375Notes

Reaction equation

HRID 390375 reaction equation
[CH3:1][Mg]Cl.[O:4]=[C:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[CH2:7][CH2:6]1.[Cl-].[NH4+]>O1CCCC1>[OH:4][C:5]1([CH3:1])[CH2:6][CH2:7][N:8]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[CH2:9][CH2:10]1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 643496Benzyl 4-oxopiperidine-1-carboxylateHCID 178418332HCID 178418332, compound2×

Product 1

HCID 10514757Benzyl 4-hydroxy-4-methylpiperidine-1-carboxylateYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Methylmagnesium chloride (9.53 mL, 3.0M tetrahydrofuran solution) was added to tetrahydrofuran (45.5 mL). Benzyl 4-oxopiperidine-1-carboxylate (5.00 g) was dissolved in tetrahydrofuran (8.8 mL), and added dropwise to a solution of ice-cooled methylmagnesium chloride in tetrahydrofuran, and the mixture was stirred at room temperature for 14 hr. The reaction mixture was ice-cooled, aqueous ammonium chloride solution (ammonium chloride 1.41 g, water 15 mL) was added dropwise, and the mixture was partitioned and extracted with ethyl acetate. The aqueous layer was extracted with ethyl acetate, and the combined organic layer was dried over magnesium sulfate, and purified by NH-silica gel column chromatography [developing solvent; hexane:ethyl acetate=80:20 (volume ratio)→60:40 (volume ratio)]. The obtained solid was washed with isopropyl ether, and dried under reduced pressure to give the title compound (4.20 g, yield 79%) as a colorless solid.

Workup

  1. additionadded dropwise to a solution of ice-
  2. temperaturecooled
  3. customthe mixture was partitioned
  4. extractionextracted with ethyl acetate
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialthe combined organic layer was dried over magnesium sulfate
  7. custompurified by NH-silica gel column chromatography [
  8. washThe obtained solid was washed with isopropyl ether
  9. customdried under reduced pressure

Sources & evidence

ORD record
ord-9a2c0b158d294de2ba1d8bd97e925c3b
Source dataset
uspto-grants-2013_02
Patent number
US08383647B2

Reaction notes

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