2,3-Difluorobenzaldehyde → tert-Butyl 1-(2,3-difluorobenzyl)-5-oxo-4-(2,2,2-trifluoroethyl)-1,4-diazepan-6-ylcarbamate

HRID 20179

Reaction equation

HRID 20179 reaction equation
[O:1]=[C:2]1[N:8]([CH2:9][C:10]([F:13])([F:12])[F:11])[CH2:7][CH2:6][NH:5][CH2:4][CH:3]1[NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18].[F:22][C:23]1[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:24]=1[CH:25]=O.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>CO.C(O)(=O)C>[F:22][C:23]1[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:24]=1[CH2:25][N:5]1[CH2:4][CH:3]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:18])([CH3:20])[CH3:19])[C:2](=[O:1])[N:8]([CH2:9][C:10]([F:11])([F:12])[F:13])[CH2:7][CH2:6]1

Participants

7

Reactant 4

HCID 1376642,3-DifluorobenzaldehydeHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 66939478tert-Butyl 7-oxo-1-(2,2,2-trifluoroethyl)-1,4-diazepan-6-ylcarbamate

Product 1

HCID 68433007tert-Butyl 1-(2,3-difluorobenzyl)-5-oxo-4-(2,2,2-trifluoroethyl)-1,4-diazepan-6-ylcarbamateYield 88.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

A mixture of tert-butyl 7-oxo-1-(2,2,2-trifluoroethyl)-1,4-diazepan-6-ylcarbamate (51 mg, 0.16 mmol), 2,3-difluorobenzaldehyde (0.053 mL, 0.49 mmol), and sodium cyanoborohydride (31 mg, 0.49 mmol) in methanol (5 mL) was adjusted to pH 4 with acetic acid. After 0.5 h, saturated aqueous sodium bicarbonate was added and the mixture was extracted with dichloromethane (3×). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated. Purification by silica gel chromatography [100% dichloromethane→95% dichloromethane/5% (10% ammonium hydroxide/methanol)] gave the title compound (62 mg). MS 438 (M+1).

Workup

  1. extractionthe mixture was extracted with dichloromethane (3×)
  2. dry with materialThe combined organic extracts were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by silica gel chromatography [100% dichloromethane→95% dichloromethane/5% (10% ammonium hydroxide/methanol)]

Sources & evidence

ORD record
ord-01f51043ad52477d81f45ae29ff9fad2
Source dataset
uspto-grants-2010_06
Patent number
US07745427B2

Linked notes

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