1,1'-Carbonyldiimidazole → N-tert-butyloxycarbonyl-4-(4-amino-5-chloro-2-methoxyphenylcarbonylaminomethyl)piperidine

HRID 1835253Notes

Reaction equation

HRID 1835253 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:13][C:14]1[C:22]([Cl:23])=[CH:21][C:17]([C:18]([OH:20])=O)=[C:16]([O:24][CH3:25])[CH:15]=1.[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([CH2:39][NH2:40])[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27]>CN(C)C=O>[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([CH2:39][NH:40][C:18]([C:17]2[CH:21]=[C:22]([Cl:23])[C:14]([NH2:13])=[CH:15][C:16]=2[O:24][CH3:25])=[O:20])[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 816264-Amino-5-chloro-2-methoxybenzoic acidHCID 7368171-Boc-4-(aminomethyl)piperidine

Product 1

HCID 11200348N-tert-butyloxycarbonyl-4-(4-amino-5-chloro-2-methoxyphenylcarbonylaminomethyl)piperidineYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

1,1′-Carbonyldiimidazole (1.61 g, 9.91 mmol) was added to a solution of 4-amino-5-chloro-2-methoxybenzoic acid (2.0 g, 9.91 mmol) in dimethylformamide (5 ml). After stirring for 5 min. at room temperature, solution of N-tert-butyloxycarbonyl-4-(aminomethyl)piperidine (1.77 g, 8.26 mmol) in dimethylformamide (5 ml) was added and the reaction mixture was heated at 55° C. After 23 h, the product was extracted into ethyl acetate and the organic layer was washed with aqueous sodium bicarbonate, dried over magnesium sulfate, filtered and concentrated. Flash chromatography of the crude product with 2:1, ethyl acetate/hexanes as the eluant gave N-tert-butyloxycarbonyl-4-(4-amino-5-chloro-2-methoxyphenylcarbonylaminomethyl)piperidine (2.63 g) as a foam.

Workup

  1. temperaturethe reaction mixture was heated at 55° C
  2. waitAfter 23 h
  3. extractionthe product was extracted into ethyl acetate
  4. washthe organic layer was washed with aqueous sodium bicarbonate
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-502c2fb6ab4c4a48a73a44caec2a5f57
Source dataset
uspto-grants-2004_08
Patent number
US06770650B2

Reaction notes

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