tert-Butyl 4-oxopiperidine-1-carboxylate → Tert-butyl 4-hydroxy-4-(4-methoxyphenyl)piperidine-1-carboxylate

HRID 716086Notes

Reaction equation

HRID 716086 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][CH:18]=1>C(OCC)C>[OH:1][C:2]1([C:20]2[CH:21]=[CH:22][C:17]([O:16][CH3:15])=[CH:18][CH:19]=2)[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 2

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178491912HCID 178491912, compound

Product 1

HCID 49760247Tert-butyl 4-hydroxy-4-(4-methoxyphenyl)piperidine-1-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of commercial tert-butyl 4-oxopiperidine-1-carboxylate (2.0 g, 10.0 mmol) and diethyl ether (30 ml) was cooled to 0° C. To this mixture was added dropwise a solution of (4-methoxyphenyl)magnesium bromide (0.5 M in diethyl ether, 30 ml, 15 mmol). After complete addition, the reaction mixture was allowed to warm to rt and stirred for 2 h. It was then slowly quenched with 150 ml of ice cold water and then the resulting mixture was extracted with 3×150 ml of DCM. The organic layers were combined, dried, filtered, and concentrated under vacuum. The crude product was purified by silica gel column chromatography (30:70 ethyl acetate:hexane) to provide the desired product (3.0 g, 100% yield): LC-MS (ES-API): m/z 305.5 (M−H)+; 1H NMR (400 MHz, DMSO-d6) δ 7.37 (q, J=1.0 Hz, 2H), 6.86 (q, J=1.0 Hz, 2H), 4.94 (s, 1H), 3.82 (d, J=11.5 Hz, 2H), 3.73 (s, 3H), 3.13 (br. s, 2H), 1.75 (td, J=12.9, 4.8 Hz, 2H), 1.56 (d, J=12.3 Hz, 2H), 1.41 (s, 9H).

Workup

  1. additionAfter complete addition
  2. temperatureto warm to rt
  3. customIt was then slowly quenched with 150 ml of ice cold water
  4. extractionthe resulting mixture was extracted with 3×150 ml of DCM
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe crude product was purified by silica gel column chromatography (30:70 ethyl acetate:hexane)

Sources & evidence

ORD record
ord-b58cafc4f1f14d08b60efa8476b9462d
Source dataset
uspto-grants-2015_11
Patent number
US09187506B2

Reaction notes

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