Oxalyl chloride → HCID 66816452, compound

HRID 1754913Notes

Reaction equation

HRID 1754913 reaction equation
C(Cl)(=O)C(Cl)=O.[F:7][C:8]([F:16])([F:15])[C:9]1([C:12](O)=[O:13])[CH2:11][CH2:10]1.[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][C:27]([NH2:32])([C:30]#[N:31])[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18].C(N(C(C)C)CC)(C)C>ClCCl.CN(C)C=O>[C:17]([O:21][C:22]([N:24]1[CH2:25][CH2:26][C:27]([C:30]#[N:31])([NH:32][C:12]([C:9]2([C:8]([F:16])([F:15])[F:7])[CH2:11][CH2:10]2)=[O:13])[CH2:28][CH2:29]1)=[O:23])([CH3:20])([CH3:18])[CH3:19]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 27783061-(Trifluoromethyl)cyclopropane-1-carboxylic acidHCID 22091429tert-Butyl 4-amino-4-cyanopiperidine-1-carboxylate

Product 1

HCID 66816452HCID 66816452, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent4×

Conditions

Temperature
0 °C

Procedure

Oxalyl chloride (0.20 ml, 2.3 mmol) and dimethylformamide (8 μl) were added to a solution of 1-trifluoromethyl-cyclopropanecarboxylic acid (308 mg, 2.00 mmol) in dichloromethane (2.1 ml) at 0° C. The mixture was stirred at 0° C. for 30 minutes and then stirred at room temperature for two hours. The reaction mixture was concentrated under reduced pressure. A solution of the resulting residue in dichloromethane (1.5 ml) was added dropwise to a solution of 4-amino-4-cyanopiperidine-1-carboxylic acid tert-butyl ester (377 mg, 1.67 mmol) and diisopropylethylamine (0.42 ml, 2.4 mmol) in dichloromethane (2.0 ml) over three minutes at 0° C., and the mixture was stirred at room temperature for 13 hours. The reaction mixture was diluted with dichloromethane, and the organic layer was then washed with water, dried over MgSO4 and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/1→2/1) to give 4-cyano-4-[(1-trifluoromethyl-cyclopropanecarbonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester as a colorless solid (519 mg, 86%).

Workup

  1. stirringstirred at room temperature for two hours
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. stirringthe mixture was stirred at room temperature for 13 hours
  4. washthe organic layer was then washed with water
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/1→2/1)

Sources & evidence

ORD record
ord-f5ed2378c5f64c549b88436dff7e54af
Source dataset
uspto-grants-2015_10
Patent number
US09169254B2

Reaction notes

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