Acetic Acid → 4-[{N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(3-methylamino-4-hydroxybenzyl)piperidine

HRID 279335Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][C:9]1[CH:37]=[C:36]([F:38])[C:35]([F:39])=[CH:34][C:10]=1[C:11]([NH:13][CH2:14][C:15]([NH:17][CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[C:28]([NH2:33])[CH:27]=2)[CH2:21][CH2:20]1)=[O:16])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C=O.[C:42](O)(=O)C.[BH3-]C#N.[Na+]>CO>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:37]=[C:36]([F:38])[C:35]([F:39])=[CH:34][C:10]=1[C:11]([NH:13][CH2:14][C:15]([NH:17][CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[C:28]([NH:33][CH3:42])[CH:27]=2)[CH2:21][CH2:20]1)=[O:16])=[O:12])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 60 °C

Procedure

To a mixture of 4-[{N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(3-amino-4-hydroxybenzyl)piperidine (20.4 mg, 0.037 mmol), 37% HCHO solution (3.0 mg, 0.037 mmol), acetic acid (0.10 mL) and methanol (1.3 mL) was added NaBH3CN (7.0 mg) in methanol (0.2 mL). The reaction mixture was stirred at 60° C. overnight. The mixture was cooled to room temperature, loaded onto Varian™ SCX column, and washed with CH3OH (5 mL×2). Product was eluted off using 2 N NH3 in CH3OH (8 mL) and concentrated to give 4-[{N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(3-methylamino-4-hydroxybenzyl)piperidine.

Workup

temperatureThe mixture was cooled to room temperature
washwashed with CH3OH (5 mL×2)
washProduct was eluted off
concentrationconcentrated

Sources & evidence

ORD record: ord-67013576c81549378f21a54b6031f4a3
Source dataset: uspto-grants-2002_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06362177B1

Reaction notes

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