Carbon tetrabromide → rac-1-[1-(3-Nitro-phenyl)-propyl]-piperidine-4-carboxylic acid cyclohexylamide

HRID 1486710Notes

Reaction equation

HRID 1486710 reaction equation
[CH2:1]([CH:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([N+:11]([O-:13])=[O:12])[CH:6]=1)O)[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(Br)(Br)(Br)Br.Cl.[CH:39]1([NH:45][C:46]([CH:48]2[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]2)=[O:47])[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH:39]1([NH:45][C:46]([CH:48]2[CH2:49][CH2:50][N:51]([CH:3]([C:5]3[CH:10]=[CH:9][CH:8]=[C:7]([N+:11]([O-:13])=[O:12])[CH:6]=3)[CH2:1][CH3:2])[CH2:52][CH2:53]2)=[O:47])[CH2:40][CH2:41][CH2:42][CH2:43][CH2:44]1

Participants

7

Reactant 5

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 81531DiisopropylethylamineHCID 105116081-(3-Nitrophenyl)propan-1-olHCID 44630870N-cyclohexylpiperidine-4-carboxamide hydrochloride

Product 1

HCID 131736800rac-1-[1-(3-Nitro-phenyl)-propyl]-piperidine-4-carboxylic acid cyclohexylamideYield 16%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of α-ethyl-3-nitro-benzenemethanol (0.54 g, 2.98 mmol) in DCM (10 mL) is treated with PPh3 (1.6 g, 6.1 mmol).) and CBr4 (2 g, 6.03 mmol). The yellowish solution is stirred at RT for 2 h 30. Piperidine-4-carboxylic acid cyclohexylamide hydrochloride J-1 (0.82 g) is added at once, as well as DIPEA (2 mL). The RM is stirred at RT overnight then heated to 70° C. for 1H. The RM is evaporated under reduced pressure. The residue is partitioned between DCM (25 mL) and sat. aq. NaHCO3 (25 mL). The organic layer is washed twice with sat. aq. NaHCO3, dried over MgSO4 and evaporated under reduced pressure. The crude residue is purified by flash chromatography on silica gel using a gradient of DCM/MeOH/NH4OH 95:5:1 to 90:10:1. After concentration of the product-containing fractions, the title compound (0.173 g, 16%) is obtained as a colorless solid LC-MS A: tR=0.68 min; [M+H]+=374.21.

Workup

  1. stirringThe RM is stirred at RT overnight
  2. temperaturethen heated to 70° C. for 1H
  3. customThe RM is evaporated under reduced pressure
  4. customThe residue is partitioned between DCM (25 mL) and sat. aq. NaHCO3 (25 mL)
  5. washThe organic layer is washed twice with sat. aq. NaHCO3
  6. dry with materialdried over MgSO4
  7. customevaporated under reduced pressure
  8. customThe crude residue is purified by flash chromatography on silica gel using a gradient of DCM/MeOH/NH4OH 95:5:1 to 90:10:1

Sources & evidence

ORD record
ord-9679c64af3884cb5b0a8373de505dcc1
Source dataset
uspto-grants-2016_08
Patent number
US09428456B2

Reaction notes

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