Tert-butyl 4-hydroxypiperidine-1-carboxylate → HCID 44128630, compound

HRID 1627601Notes

Reaction equation

HRID 1627601 reaction equation
CC(C)([O-])C.[K+].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH:17]([OH:20])[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].F[C:22]1[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[C:24]([CH3:30])[CH:23]=1>CCOCC>[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH:17]([O:20][C:22]2[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[C:24]([CH3:30])[CH:23]=2)[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:8])[CH3:9]

Participants

5

Reactant 3

HCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 38260554-Fluoro-2-methylbenzonitrileHCID 23665647Potassium tert-butoxide

Product 1

HCID 44128630HCID 44128630, compoundYield 115.3%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

22.6 g Potassium tert. butoxide, 33.2 g 4-Hydroxy-piperidine-1-carboxylic acid tert-butyl ester and 300 mL MTB ether were stirred for 1 h at reflux. A solution of 20.3 g 4-Fluoro-2-methyl-benzonitrile, dissolved in 250 mL MTB ether was added within 20 min to the suspension and heating to reflux was continued for 7 h. The reaction was quenched with water. The organic layer was separated and washed with water and concentrated to give 54.8 g (yield 92%) of 4-(4-Cyano-3-methyl-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester. 1H NMR (500 MHz, d6-DMSO) δ 1.40 (s, 9H), 1.47-1.55 (m, 2H), 1.88-1.95 (m, 2H), 2.43 (s, 3H), 3.13-3.22 (m, 2H), 3.63-3.70 (m, 2H), 4.66-4.73 (m, 1H), 6.96 (dd, J=8.6, 2.4 Hz, 1H), 7.07 (d, J=2.3 Hz, 1H), 7.67 (d, J=8.7 Hz, 1H).

Workup

  1. temperatureat reflux
  2. additionwas added within 20 min to the suspension
  3. temperatureheating
  4. temperatureto reflux
  5. customThe reaction was quenched with water
  6. customThe organic layer was separated
  7. washwashed with water
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-a74ff8822e1146c8bef0862e866e6577
Source dataset
uspto-grants-2014_07
Patent number
US08785642B2

Reaction notes

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