Methanol → (S)-4-([1,4]oxazepan-6-yl)benzonitrile

HRID 515466Notes

Reaction equation

HRID 515466 reaction equation
C1([C@H]([N:9]2[CH2:15][C@H:14]([C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=3)[CH2:13][O:12][CH2:11][CH2:10]2)C)C=CC=CC=1.ClC(OC(Cl)C)=O.CO>ClCCCl>[O:12]1[CH2:13][C@@H:14]([C:16]2[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=2)[CH2:15][NH:9][CH2:10][CH2:11]1

Participants

5

Reactant 3

HCID 887MethanolHCID 5213051-Chloroethyl chloroformateHCID 67283020(S)-4-(4-((R)-1-phenylethyl)-[1,4]oxazepan-6-yl)benzonitrile

Product 1

HCID 67281424(S)-4-([1,4]oxazepan-6-yl)benzonitrileYield 71.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of (S)-4-(4-((R)-1-phenylethyl)-[1,4]oxazepan-6-yl)benzonitrile (0.662 g, 2.16 mmol) in 1,2-dichloroethane (3.60 ml) was added 1-chloroethyl chloroformate (0.772 g, 5.40 mmol) at room temperature. The mixture was refluxed for 8 hours. Methanol (15 ml) was added to the mixture cooled to room temperature. The mixture was refluxed again for 2 hours. The mixture was concentrated in vacuo. The residue was partitioned between aqueous sodium hydrogen carbonate and chloroform. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluent: chloroform/methanol=96/4) to afford (S)-4-([1,4]oxazepan-6-yl)benzonitrile as pale yellow solid (312 mg, 70%).

Workup

  1. temperatureThe mixture was refluxed for 8 hours
  2. temperatureThe mixture was refluxed again for 2 hours
  3. concentrationThe mixture was concentrated in vacuo
  4. customThe residue was partitioned between aqueous sodium hydrogen carbonate and chloroform
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography (eluent: chloroform/methanol=96/4)

Sources & evidence

ORD record
ord-11a78b63f71d4cea9be8990abc8f54c6
Source dataset
uspto-grants-2015_08
Patent number
US09108957B2

Reaction notes

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