Sodium Carbonate → (S)-4-(4-((R)-1-phenylethyl)-[1,4]oxazepan-6-yl)benzonitrile

HRID 515465Notes

Reaction equation

HRID 515465 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:14][O:13][CH2:12][CH2:11][N:10]([C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:16])[CH2:9]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:29][N:30](C)C(=O)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.O.O.O.[K+].[K+].[K+].[K+].[Fe+2].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>[C:17]1([C@H:15]([N:10]2[CH2:9][C@H:8]([C:5]3[CH:6]=[CH:7][C:2]([C:29]#[N:30])=[CH:3][CH:4]=3)[CH2:14][O:13][CH2:12][CH2:11]2)[CH3:16])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 31374DimethylacetamideHCID 67281235(S)-6-(4-bromophenyl)-4-((R)-1-phenylethyl)-[1,4]oxazepane

Product 1

HCID 67283020(S)-4-(4-((R)-1-phenylethyl)-[1,4]oxazepan-6-yl)benzonitrileYield 53%

Reagents, catalysts & solvents 3

HCID 161067Potassium ferrocyanide trihydrateCatalystHCID 167845palladium(II) acetateCatalyst2×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalyst2×

Conditions

Temperature
120 °C

Procedure

To a solution of (S)-6-(4-bromophenyl)-4-((R)-1-phenylethyl)-[1,4]oxazepane (1.48 g, 4.11 mmol) in N,N-dimethylacetamide (6.9 ml) was added sodium carbonate (0.436 g, 4.11 mmol), palladium acetate (18.4 mg, 0.082 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (78.4 mg, 0.164 mmol), potassium hexacyanoferrate(II) trihydrate (0.521 g, 1.23 mmol) at room temperature under nitrogen atmosphere. The mixture was heated to 120° C. Additional palladium acetate (18.4 mg, 0.082 mmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (78.4 mg, 0.164 mmol) was added twice to the reaction mixture every one hour. After one hour from last addition of the catalyst, the mixture was filtered through a pad of Celite to remove solid materials and partitioned between water and ethyl acetate. The organic layer was washed with water, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluant: hexane/ethyl acetate=7/3) to afford (S)-4-(4-((R)-1-phenylethyl)-[1,4]oxazepan-6-yl)benzonitrile as pale yellow solid (662 mg, 53%).

Workup

  1. additionAfter one hour from last addition of the catalyst
  2. filtrationthe mixture was filtered through a pad of Celite
  3. customto remove solid materials
  4. custompartitioned between water and ethyl acetate
  5. washThe organic layer was washed with water
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel column chromatography (eluant: hexane/ethyl acetate=7/3)

Sources & evidence

ORD record
ord-f5ca03e89a5b4504865621e388a65a7b
Source dataset
uspto-grants-2015_08
Patent number
US09108957B2

Reaction notes

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