Dimethylformamide → Tert-butyl 9-cyano-2,3-dihydrobenzo[F][1,4]oxazepine-4(5H)-carboxylate

HRID 1514227Notes

Reaction equation

HRID 1514227 reaction equation
Br[C:2]1[C:12]2[O:11][CH2:10][CH2:9][N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH3:20][N:21](C)C=O>C(OCC)(=O)C.[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:20]([C:2]1[C:12]2[O:11][CH2:10][CH2:9][N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1)#[N:21]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 59403519Tert-butyl 9-bromo-2,3-dihydrobenzo[F][1,4]oxazepine-4(5H)-carboxylate

Product 1

HCID 54757009Tert-butyl 9-cyano-2,3-dihydrobenzo[F][1,4]oxazepine-4(5H)-carboxylate

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1,1-dimethylethyl 9-bromo-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (Preparation 101) (1.34 g, 4.08 mmol) in N,N-dimethylformamide (11 ml) was degassed under vacuum (3 mm Hg) for 15 min then stirred under nitrogen. Zinc cyanide (575 mg, 4.90 mmol) then tetrakis(triphenylphosphine) palladium(0) (472 mg, 0.41 mmol) were added and the resulting mixture was stirred at 100° C. under nitrogen overnight then diluted with ethyl acetate. The insoluble residues were filtered off and washed with ethyl acetate, bleached for two days washed twice with brine, dried over magnesium sulphate and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel, eluting with 15-45% ethyl acetate in cyclohexane gave the title compound as a colourless solid (980 mg). MS (ES) C15H18N2O3 requires 274 found 275 [M+H]+.

Workup

  1. stirringthe resulting mixture was stirred at 100° C. under nitrogen overnight
  2. filtrationThe insoluble residues were filtered off
  3. washwashed with ethyl acetate, bleached for two days
  4. washwashed twice with brine
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by flash chromatography on silica gel
  8. washeluting with 15-45% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-191a6877f4294a25a7480b29a2d2e0cb
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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