Diisopropylethylamine → tert-Butyl 4-(3-(tert-butylcarbamoyl)benzyl)-1,4-diazepane-1-carboxylate

HRID 1878377Notes

Reaction equation

HRID 1878377 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:15]([NH:19][C:20](=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27]Cl)[CH:22]=1)([CH3:18])([CH3:17])[CH3:16].C(N(C(C)C)C(C)C)C>O1CCCC1.ClCCl>[C:15]([NH:19][C:20]([C:21]1[CH:22]=[C:23]([CH:24]=[CH:25][CH:26]=1)[CH2:27][N:11]1[CH2:12][CH2:13][CH2:14][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]1)=[O:29])([CH3:18])([CH3:16])[CH3:17]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 43156221N-tert-butyl-3-(chloromethyl)benzamide

Product 1

HCID 57917580tert-Butyl 4-(3-(tert-butylcarbamoyl)benzyl)-1,4-diazepane-1-carboxylateYield 89.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl-1-homopiperazine carboxylate (0.25 g, 1.25 mmol) and N-tert-butyl-3-(chloromethyl)benzamide (0.470 g, 1.25 mmol) in tetrahydrofuran (4 mL) was added N-ethyl-N-isopropylpropan-2-amine (0.33 mL, 1.88 mmol). The resultant mixture was stirred at 80° C. for 16 hours. The mixture was cooled to room temperature, diluted with dichloromethane (50 mL) and washed with saturated ammonium chloride (aqueous) and brine. The organic phase was dried (sodium sulfate), filtered and concentrated under vacuum. The residue was purified by column chromatography on silica (using a solvent gradient of dichloromethane/methanol) to afford the title compound (0.435 g) as a white solid. MS (ESI) m/z 389.9 [M+H]+

Workup

  1. washwashed with saturated ammonium chloride (aqueous) and brine
  2. dry with materialThe organic phase was dried (sodium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by column chromatography on silica (

Sources & evidence

ORD record
ord-4fc1979e12fe4e018e0ce6ec98e412a4
Source dataset
uspto-grants-2012_11
Patent number
US08314091B2

Reaction notes

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