Triphenylphosphine → 4-Methyl-4-(2-trifluoromethylphenoxy)piperidine

HRID 552141Notes

Reaction equation

HRID 552141 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([OH:15])([CH3:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:23]([F:26])([F:25])[F:24].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1(C)C=CC=CC=1>[CH3:14][C:11]1([O:15][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[C:23]([F:26])([F:25])[F:24])[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1.[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH3:14])([O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[C:23]([F:24])([F:25])[F:26])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 679582-TrifluoromethylphenolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 22730812tert-Butyl 4-hydroxy-4-methylpiperidine-1-carboxylate

Product 2

HCID 671715074-Methyl-4-(2-trifluoromethylphenoxy)piperidineHCID 671718194-Methyl-4-(2-trifluoromethylphenoxy)piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred solution of 4-hydroxy-4-methylpiperidine-1-carboxylic acid tert-butyl ester (0.500 g, 2.32 mmol) in toluene (10 mL) was added 2-hydroxybenzotrifluoride (0.414 g, 2.56 mmol), triphenylphosphine (0.682 g, 2.555 mmol) and diethyl azocarboxylate (0.5 mL, 2.56 mmol). The resulting mixture was stirred at reflux for 18 hours. Toluene was removed in vacuo and the obtained crude product was purified by column chromatography to yield the desired product, 4-methyl-4-(2-trifluoromethyl-phenoxy)piperidine-1-carboxylic acid tert-butyl ester, in 5% yield (0.025 g). 1H NMR (300 MHz, CDCl3) δ 7.57-7.54 (m, 1H), 7.41-7.36 (m, 1H), 7.09 (d, J=7.9 Hz, 1H), 7.02-6.97 (m, 1H), 3.81-3.76 (m, 2H), 3.28 (t, J=11.9 Hz, 2H), 2.15-2.11 (m, 2H), 1.67-1.58 (m, 2H), 1.44 (s, 9H), 1.39 (s, 3H).

Workup

  1. temperatureat reflux for 18 hours
  2. customToluene was removed in vacuo
  3. customthe obtained crude product
  4. customwas purified by column chromatography

Sources & evidence

ORD record
ord-f14273d3edce4387ab57b9a1ac94a29d
Source dataset
uspto-grants-2011_05
Patent number
US07951805B2

Reaction notes

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