Water → 4-[4-((R)-1-phenyl-ethyl)-[1,4]oxazepan-7-yl]-benzonitrile

HRID 515480Notes

Reaction equation

HRID 515480 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:14][CH2:13][CH2:12][N:11]([C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.O.[CH3:24][N:25](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2]>[C:17]1([C@H:15]([N:11]2[CH2:10][CH2:9][CH:8]([C:5]3[CH:6]=[CH:7][C:2]([C:24]#[N:25])=[CH:3][CH:4]=3)[O:14][CH2:13][CH2:12]2)[CH3:16])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 962WaterHCID 6228DimethylformamideHCID 672813307-(4-bromo-phenyl)-4-((R)-1-phenyl-ethyl)-[1,4]oxazepane

Product 1

HCID 672813254-[4-((R)-1-phenyl-ethyl)-[1,4]oxazepan-7-yl]-benzonitrile

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 15826098Cyclopenta-1,3-diene;cyclopenta-2,4-dien-1-yl(diphenyl)phosphane;iron(2+)Catalyst

Conditions

Temperature
120 °C

Procedure

A mixture of diastereopure 7-(4-bromo-phenyl)-4-((R)-1-phenyl-ethyl)-[1,4]oxazepane (diastereomer type A) (2.0 g, 5.6 mmol), zinc(II) cyanide (0.40 g, 3.4 mmol), tris(dibenzylideneacetane)dipalladium (0.46 g, 0.50 mmol), diphenylphosphinoferrocene (0.67 g, 1.2 mmol) and water (0.02 mL, 1.0 mmol) in dimethylformamide (10 mL) was prepared at room temperature under nitrogen atmosphere. The mixture was heated to 120° C. and stirred for 8 hours. After cooling to room temperature, the reaction was quenched by the addition of 2N ammonia aqueous solution and diluted with ethyl acetate. The organic layer was separated and dried over anhydrous sodium sulfate. Concentration of the solution followed by purification of the residue by flash column chromatography on silica gel (hexane/ethyl acetate=90/10 to 60/40 as eluants) was yield 4-[4-((R)-1-phenyl-ethyl)-[1,4]oxazepan-7-yl]-benzonitrile (diastereomer type A) (0.68 g, 2.2 mmol, 40%) as brown oil.

Workup

  1. customwas prepared at room temperature under nitrogen atmosphere
  2. temperatureAfter cooling to room temperature
  3. customthe reaction was quenched by the addition of 2N ammonia aqueous solution
  4. additiondiluted with ethyl acetate
  5. customThe organic layer was separated
  6. dry with materialdried over anhydrous sodium sulfate
  7. customConcentration of the solution followed by purification of the residue by flash column chromatography on silica gel (hexane/ethyl acetate=90/10 to 60/40 as eluants)

Sources & evidence

ORD record
ord-5a5ee6f888dd4327a1af36e21b66d552
Source dataset
uspto-grants-2015_08
Patent number
US09108957B2

Reaction notes

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