Water → tert-Butyl 8-isopropoxy-2,3-dihydropyrido[3,2-f][1,4]oxazepine-4(5H)-carboxylate

HRID 2191253Notes

Reaction equation

HRID 2191253 reaction equation
[CH:1]([OH:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:8]1[CH:9]=[CH:10][C:11]2[CH2:12][N:13]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14][CH2:15][O:16][C:17]=2[N:18]=1.O>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC(C)=CC=2)C2C=CC(C)=CC=2)C2C=CC(C)=CC=2)=CC=1>[CH:1]([O:4][C:8]1[CH:9]=[CH:10][C:11]2[CH2:12][N:13]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14][CH2:15][O:16][C:17]=2[N:18]=1)([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 962WaterHCID 3776IsopropanolHCID 24758Sodium hydrideHCID 57356939Tert-butyl 8-chloro-2,3-dihydropyrido[3,2-F][1,4]oxazepine-4(5H)-carboxylate

Product 1

HCID 68429626tert-Butyl 8-isopropoxy-2,3-dihydropyrido[3,2-f][1,4]oxazepine-4(5H)-carboxylateYield 64%

Reagents, catalysts & solvents 3

HCID 4189906(S)-(-)-2,2'-Bis(di-p-tolylphosphino)-1, 1'-binaphthylCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
70 °C

Procedure

To a solution of isopropyl alcohol (0.081 mL) in toluene (2 mL) was added sodium hydride (0.084 g), and the resulting mixture was stirred at 70° C. for 15 min under a nitrogen atmosphere. A mixture of tert-butyl 8-chloro-2,3-dihydropyrido[3,2-f][1,4]oxazepine-4(5H)-carboxylate (0.30 g), (S)-tol-BINAP (0.022 g), Pd2(dba)3 (0.015 g) and toluene (2 mL) was added, and the resulting mixture was stirred at 100° C. for 16 hr under an argon atmosphere. The reaction solution was poured into water, and the resulting product was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (solvent gradient; 0→40% ethyl acetate/hexane) to give tert-butyl 8-isopropoxy-2,3-dihydropyrido[3,2-f][1,4]oxazepine-4(5H)-carboxylate (0.21 g, 64%) as a colorless oil.

Workup

  1. additionwas added
  2. stirringthe resulting mixture was stirred at 100° C. for 16 hr under an argon atmosphere
  3. extractionthe resulting product was extracted with ethyl acetate
  4. washThe organic layer was washed with water and saturated brine
  5. customdried
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (solvent gradient; 0→40% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-65f03c7e3b0a4cef9c800b50dbc29045
Source dataset
uspto-grants-2012_12
Patent number
US08329687B2

Reaction notes

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