Borane,N-dimethylmethanamine (1:1) → 2-(1-Boc-piperidin-4-ylmethylamino)-N-(5-chloropyridin-2-yl)-5-fluorobenzamide

HRID 1247062Notes

Reaction equation

HRID 1247062 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]=[N:15][C:16]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:17]=2[C:18]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][N:22]=2)=[O:19])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[B-][N+](C)(C)C>C(O)(=O)C>[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:17]=2[C:18]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][N:22]=2)=[O:19])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]

Participants

4

Reactant 2

HCID 6327651Borane,N-dimethylmethanamine (1:1)HCID 219061692-(1-Boc-piperidin-4-ylmethylidene)amino-N-(5-chloropyridin-2-yl)-5-fluorobenzamide

Product 1

HCID 219066432-(1-Boc-piperidin-4-ylmethylamino)-N-(5-chloropyridin-2-yl)-5-fluorobenzamideYield 97%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
70 °C

Procedure

A solution containing 2-(1-Boc-piperidin-4-ylmethylidene)amino-N-(5-chloropyridin-2-yl)-5-fluorobenzamide from above (6.0 g, 13 mmol) and borane trimethylamine complex (2.9 g, 39 mmol) in glacial acetic acid (100 mL) was heated at 70° C. for 24 h. The solution was allowed to cool to room temperature; then the solvent was removed in vacuo, and the residue was partitioned between dichloromethane (200 mL) and water (100 mL). The biphasic mixture was treated with 2 N NaOH until neutral; then the organic layer was separated and the aqueous layer was washed again with dichloromethane (100 mL). The combined organic layers were washed with brine (100 mL), dried with MgSO4, and filtered. The filtrate was concentrated in vacuo to give 5.85 g (97%) of the title compound as an orange foam which was used directly in the next step without further purification.

Workup

  1. temperatureto cool to room temperature
  2. customthen the solvent was removed in vacuo
  3. customthe residue was partitioned between dichloromethane (200 mL) and water (100 mL)
  4. additionThe biphasic mixture was treated with 2 N NaOH until neutral
  5. customthen the organic layer was separated
  6. washthe aqueous layer was washed again with dichloromethane (100 mL)
  7. washThe combined organic layers were washed with brine (100 mL)
  8. dry with materialdried with MgSO4
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-d62d398a68d2441896bac0d449d84a3d
Source dataset
uspto-grants-2006_10
Patent number
US07129245B2

Reaction notes

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