tert-Butyl 4-oxopiperidine-1-carboxylate → tert-Butyl 4-hydroxy-4-(2-methylphenyl)piperidine-1-carboxylate

HRID 1990906Notes

Reaction equation

HRID 1990906 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[C:15]1([CH3:23])[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[Mg]Br>C(OCC)C.C(=O)=O.CC(C)=O>[C:4]([O:3][C:1]([N:8]1[CH2:13][CH2:12][C:11]([OH:14])([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[CH3:23])[CH2:10][CH2:9]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

5

Reactant 2

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178424303HCID 178424303, compound

Product 1

HCID 49760233tert-Butyl 4-hydroxy-4-(2-methylphenyl)piperidine-1-carboxylateYield 112.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 18522661Acetone cardiceSolvent

Procedure

N-Boc-4-piperidone (Boc-29.155) (200 mg, 11.0 mmol) was dissolved in 5 ml of anhydrous ethyl ether, cooled in dry ice/acetone bath. 2-Tolylmagnesium bromide (550 μl, 2M in ethyl ether, 1.1 mmol) was added dropwise over 5 min. White precipitate was formed. After 5 h, remove the dry ice/acetone bath and rise to room temperature gradually. After 2 h, cooled in ice bath, 8 ml of saturated NH4Cl and 2 ml of H2O were added. The organic phase was separated and aqueous phase was extracted with 4×10 ml of Et2O. Combined with organic phase and washed with 8 ml of H2O and 10 ml of brine, dried over MgSO4. Concentrated and dried to obtain 361 mg of colorless oil. Separated by silica gel to obtain 4f (229.7 mg, 79% yield) as colorless oil. 1H NMR (CDCl3, 200 MHz) δ 1.47 (s, 9H), 1.93 (m, 4H), 2.60 (s, 3H), 3.27 (t, 2H, J=13.0 Hz), 3.96 (d, 2H, J=12.2 Hz), 7.15 (m, 3H), 7.35 (m, 1H).

Workup

  1. customWhite precipitate was formed
  2. customremove the dry ice/acetone bath and rise to room temperature gradually
  3. waitAfter 2 h
  4. temperaturecooled in ice bath
  5. addition8 ml of saturated NH4Cl and 2 ml of H2O were added
  6. customThe organic phase was separated
  7. extractionaqueous phase was extracted with 4×10 ml of Et2O
  8. washwashed with 8 ml of H2O and 10 ml of brine
  9. dry with materialdried over MgSO4
  10. concentrationConcentrated
  11. customdried

Sources & evidence

ORD record
ord-9a2dab52fa5044089eea2a6600df27ed
Source dataset
uspto-grants-2010_01
Patent number
US07645754B2

Reaction notes

Loading…