1,2-Dichloroethane → 4-(4-fluoro-phenyl)-4-[(S)-1-(4-fluoro-phenyl)-ethylcarbamoyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 2189969Notes

Reaction equation

HRID 2189969 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)([C:14](O)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[F:45][C:46]1[CH:51]=[CH:50][C:49]([C@@H:52]([NH2:54])[CH3:53])=[CH:48][CH:47]=1>ClCCl.O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)([C:14](=[O:15])[NH:54][C@H:52]([C:49]2[CH:50]=[CH:51][C:46]([F:45])=[CH:47][CH:48]=2)[CH3:53])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 2779063(S)-1-(4-Fluorophenyl)-ethylamineHCID 450740231-(tert-Butoxycarbonyl)-4-(4-fluorophenyl)piperidine-4-carboxylic acid

Product 1

HCID 666711954-(4-fluoro-phenyl)-4-[(S)-1-(4-fluoro-phenyl)-ethylcarbamoyl]-piperidine-1-carboxylic acid tert-butyl esterYield 53.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

4-(4-Fluoro-phenyl)-piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (1.0 g, 3.092 mmol) (commercially available) was suspended in dichloromethane (10 mL). EDC (949 mg, 4.948 mmol), HOBT (758 mg, 4.948 mmol) and triethylamine (1.6 mL, 11.442 mmol) were added at room temperature, followed by slow addition of a solution of (S-)-1-(4-fluorophenyl)ethylamine (0.50 mL, 3.711 mmol) in dichloromethane (5 mL). The reaction mixture was stirred at room temperature for 12 h. Water was added to the reaction mixture, the aqueous phase was extracted with ethyl acetate, the organic layers were combined and washed with aqueous ammonium chloride solution and brine, dried over Na2SO4 and the solvents were evaporated. The residue was purified by flash chromatography over a 70 g silica gel column with n-heptane and ethyl acetate to give 735 mg 4-(4-fluoro-phenyl)-4-[(S)-1-(4-fluoro-phenyl)-ethylcarbamoyl]-piperidine-1-carboxylic acid tert-butyl ester. MS ISN (m/e): 433.7 [(M−H)−].

Workup

  1. extractionthe aqueous phase was extracted with ethyl acetate
  2. washwashed with aqueous ammonium chloride solution and brine
  3. dry with materialdried over Na2SO4
  4. customthe solvents were evaporated
  5. customThe residue was purified by flash chromatography over a 70 g silica gel column with n-heptane and ethyl acetate

Sources & evidence

ORD record
ord-6b0f330ebb4c4ba6a4ed5c05e9c0fd35
Source dataset
uspto-grants-2012_12
Patent number
US08324250B2

Reaction notes

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