Diethyl Ether → tert-Butyl 4-hydroxy-4-(4-methoxy-2-methylphenyl)piperidine-1-carboxylate

HRID 1507188Notes

Reaction equation

HRID 1507188 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([Mg]Br)=[CH:19][C:18]=1C.[CH2:26](OCC)C>>[OH:1][C:2]1([C:20]2[CH:19]=[CH:18][C:17]([O:16][CH3:15])=[CH:22][C:21]=2[CH3:26])[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]1

Participants

4

Reactant 3

HCID 3283Diethyl EtherHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178491913HCID 178491913, compound

Product 1

HCID 118207352tert-Butyl 4-hydroxy-4-(4-methoxy-2-methylphenyl)piperidine-1-carboxylateYield 71%

Procedure

A solution of tert-butyl 4-oxopiperidine-1-carboxylate (2 g, 10 mmol) in diethyl ether (100 mL) was chilled to 0° C., and a solution of (4-methoxy-3-methylphenyl)magnesium bromide (0.5 M in ether) (20 mL, 10 mmol) was added. The reaction mixture was allowed to warm to rt and stirred for 12 h. The reaction mixture was then quenched with a saturated NH4Cl solution and the mixture was diluted with ethyl acetate. The organic layer was separated, washed with brine, dried over anhydrous Na2SO4, and then evaporated under reduced pressure to provide the desired product (2.3 g, 71%); 1H NMR (400 MHz, DMSO-d6) δ 7.27 (d, J=8.0 Hz, 1H), 6.75-6.61 (m, 2H), 4.83 (s, 1H), 3.85-3.77 (m, 2H), 3.71 (s, 3H), 3.17 (d, J=5.0 Hz, 2H), 2.51 (s, 3H), 1.82-1.73 (m, 4H), 1.41 (s, 9H).

Workup

  1. customThe reaction mixture was then quenched with a saturated NH4Cl solution
  2. additionthe mixture was diluted with ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-4c733905fb13463f9395d87901206cef
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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