N-Methylbenzylamine → HCID 67517650, compound

HRID 919625Notes

Reaction equation

HRID 919625 reaction equation
O=[C:2]1[CH2:8][O:7][CH2:6][CH2:5][N:4]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:3]1.[CH3:16][NH:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH2:18]([N:17]([CH3:16])[CH:2]1[CH2:8][O:7][CH2:6][CH2:5][N:4]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:3]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 7669N-MethylbenzylamineHCID 5049666Sodium triacetoxyborohydrideHCID 24865325tert-Butyl 6-oxo-1,4-oxazepane-4-carboxylate

Product 1

HCID 67517650HCID 67517650, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl 6-oxo-1,4-oxazepane-4-carboxylate (1.30 g (6.04 mmol) 107.1 (prepared as described in WO2004074291) in DCM (20 mL) was treated with N-methyl-benzylamine (0.857 mL, 6.64 mmol) and stirred at rt for 30 min. Sodium triacetoxyborohydride (1.54 g, 7.25 mmol) was then added, and the reaction mixture was stirred at room temperature for 24 hr. Excess hydride was quenched by the addition of H2O and the mixture was extracted with EtOAc (2×). The combined organic layers were dried with MgSO4, filtered, and concentrated in vacuo, absorbing onto 8 g SiO2. Purification by flash column chromatography (ISCO 40 g SiO2, 20% EtOAc/Hexanes then gradient to 80% EtOAc/hexanes) afforded tert-butyl 6-(benzyl(methyl)amino)-1,4-oxazepane-4-carboxylate (0.759 g) 107.2 as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.35-7.28 (m, 4H), 7.27-7.19 (m, 1H), 4.19-4.10 (m, 1H), 4.06-4.03 (m, 1H), 3.99-3.95 (m, 1H), 3.87 (m, 1H), 3.77-3.75 (m, 2H), 3.64-3.56 (m, 1H), 3.50 (ddd, J=3.0, 9.9, 12.5 Hz, 1H), 3.26-3.12 (m, 2H), 3.11-2.98 (m, 1H), 2.33-2.22 (m, 3H), 1.53-1.33 (m, 9H); LCMS (ESI) m/z: 321.20 [M+H]+.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 24 hr
  2. customExcess hydride was quenched by the addition of H2O
  3. extractionthe mixture was extracted with EtOAc (2×)
  4. dry with materialThe combined organic layers were dried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customabsorbing onto 8 g SiO2
  8. customPurification by flash column chromatography (ISCO 40 g SiO2, 20% EtOAc/Hexanes

Sources & evidence

ORD record
ord-9999b720ad5845d0bef72f4fb1ed17b5
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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