Oxalyl chloride → HCID 59822488, compound

HRID 2425765Notes

Reaction equation

HRID 2425765 reaction equation
[CH:1]([N:4]1[C:13]2[C:8](=[C:9]([CH3:14])[CH:10]=[CH:11][CH:12]=2)[CH:7]=[C:6]([C:15]([OH:17])=O)[C:5]1=[O:18])([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.[NH2:25][CH2:26][CH:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1.C(N(C(C)C)CC)(C)C>ClCCl.CN(C)C=O>[CH:1]([N:4]1[C:13]2[C:8](=[C:9]([CH3:14])[CH:10]=[CH:11][CH:12]=2)[CH:7]=[C:6]([C:15]([NH:25][CH2:26][CH:27]2[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]2)=[O:17])[C:5]1=[O:18])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 7368171-Boc-4-(aminomethyl)piperidineHCID 59822466HCID 59822466, compound

Product 1

HCID 59822488HCID 59822488, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of 1-isopropyl-5-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid (8.00 g, 32.6 mmol, step 4 in preparation 2) in dichloromethane (200 mL) was added dropwise oxalyl chloride (8.5 mL, 98 mmol) at 0° C. Then, N,N-dimethylformamide (3 drops) was carefully added to the mixture. The resulting mixture was stirred at 0° C. for 30 min and at room temperature for 3 h. Then, the mixture was evaporated in vacuo to give crude acid chloride as a yellow solid. Then, to a mixture of tert-butyl 4-(aminomethyl)piperidine-1-carboxylate (9.08 g, 42.4 mmol) and diisopropylethylamine (11.4 mL, 65.2 mmol) in dichloromethane (200 mL) was added dropwise a solution of crude acid chloride in dichloromethane (50 mL) at 0° C., and the mixture was stirred at room temperature for 3 h. The resulting mixture was poured onto water (300 mL), and the aqueous layer was extracted with dichloromethane (200 mL×3). The combined organic layer was dried over magnesium sulfate, and concentrated in vacuo. The residue was chromatographed on a column of silica gel with ethyl acetate/hexane (1/1.5) and then methanol/dichloromethane (1/40˜1/10) to give 15.0 g (quant.) of the title compound as a pale yellow solid.

Workup

  1. customThen, the mixture was evaporated in vacuo
  2. customto give crude acid chloride as a yellow solid
  3. stirringthe mixture was stirred at room temperature for 3 h
  4. additionThe resulting mixture was poured onto water (300 mL)
  5. extractionthe aqueous layer was extracted with dichloromethane (200 mL×3)
  6. dry with materialThe combined organic layer was dried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was chromatographed on a column of silica gel with ethyl acetate/hexane (1/1.5)

Sources & evidence

ORD record
ord-1d4ae374cc6e4720906adb4f92771029
Source dataset
uspto-grants-2011_06
Patent number
US07964727B2

Reaction notes

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