1-Bromo-2-methylpropane → (S)-tert-Butyl 1-isobutyl-2-oxoazepan-3-ylcarbamate

HRID 529563Notes

Reaction equation

HRID 529563 reaction equation
[O:1]=[C:2]1[C@@H:8]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:7][CH2:6][CH2:5][CH2:4][NH:3]1.[H-].[Na+].[CH2:19](Br)[CH:20]([CH3:22])[CH3:21].[NH4+].[Cl-]>CN(C=O)C>[CH2:19]([N:3]1[CH2:4][CH2:5][CH2:6][CH2:7][C@H:8]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:15])[CH3:14])[C:2]1=[O:1])[CH:20]([CH3:22])[CH3:21]

Participants

6

Reactant 4

HCID 65551-Bromo-2-methylpropaneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 7022178(S)-tert-Butyl (2-oxoazepan-3-yl)carbamate

Product 1

HCID 68310529(S)-tert-Butyl 1-isobutyl-2-oxoazepan-3-ylcarbamateYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-tert-butyl 2-oxoazepan-3-ylcarbamate (116 mg, 0.510 mmol) in DMF (2 mL) at 0° C. was added sodium hydride (60% in oil, 23 mg, 0.57 mmol) in 2 portions. After stirring for 5 min, isobutyl bromide (175 mg, 1.28 mmol) was added to the reaction mixture and the mixture was stirred at rt for 20 h. Saturated aqueous NH4Cl (2 mL) was added to the mixture and crude product was extracted with methylene chloride (3 mL) and the combined organic layers were dried (Na2SO4) and concentrated. The crude product was purified using silica gel chromatography to afford (S)-tert-Butyl 1-isobutyl-2-oxoazepan-3-ylcarbamate (46.4 mg, 0.247 mmol, 49% yield). Anal. Calcd. for C15H28N2O3 m/z 284.2. found: 285.2 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 6.44 (d, J=6.64 Hz, 1H), 4.26 (t, J=9 Hz, 1H), 3.57-3.50 (m, 1H), 3.26-3.17 (m, 2H), 3.10-3.05 (m, 1H), 1.84-1.62 (m, 5H), 1.37 (s, 9H), 1.34-1.24 (m, 2H), 0.84-0.80 (m, 6H).

Workup

  1. stirringthe mixture was stirred at rt for 20 h
  2. extractionwas extracted with methylene chloride (3 mL)
  3. dry with materialthe combined organic layers were dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe crude product was purified

Sources & evidence

ORD record
ord-7bb752e53f454cb3869c006670397167
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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