2-Nitrophenyl selenocyanate → rel-(3S,5S)-7-Chloro-5-(2-cyclopropylethynyl)-1,5-dihydro-3-ethen yl-5-(trifluoromethyl)-4,1-benzoxazepin-2(3H)-one

HRID 2296701Notes

Reaction equation

HRID 2296701 reaction equation
[N+](C1C=CC=CC=1[Se]C#N)([O-])=O.[BH4-].[Na+].Br[CH2:16][CH2:17][C@@H:18]1[O:24][C@:23]([C:29]#[C:30][CH:31]2[CH2:33][CH2:32]2)([C:25]([F:28])([F:27])[F:26])[C:22]2[CH:34]=[C:35]([Cl:38])[CH:36]=[CH:37][C:21]=2[NH:20][C:19]1=[O:39]>C1COCC1.C(O)C>[Cl:38][C:35]1[CH:36]=[CH:37][C:21]2[NH:20][C:19](=[O:39])[C@H:18]([CH:17]=[CH2:16])[O:24][C@:23]([C:29]#[C:30][CH:31]3[CH2:33][CH2:32]3)([C:25]([F:26])([F:27])[F:28])[C:22]=2[CH:34]=1

Participants

6

Reactant 3

HCID 1039312-Nitrophenyl selenocyanateHCID 4311764Sodium borohydrideHCID 57189482rel-(3S,5S)-3-(2-Bromoethyl)-7-chloro-5-cyclopropylethynyl-1,5-dihydro-5-(trifluoromethyl)-4,1-benzoxazepin-2(3H)-one

Product 1

HCID 56994752rel-(3S,5S)-7-Chloro-5-(2-cyclopropylethynyl)-1,5-dihydro-3-ethen yl-5-(trifluoromethyl)-4,1-benzoxazepin-2(3H)-oneYield 61.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

To a room temperature solution of 409 mg (1.8 mmol) of 2-nitrophenylselenocyanate in 5.0 mL of THF was added 16 mL of ethanol and 90 mg of sodium borohydride. After stirring 1 h, a solution of 260 mg of rel-(3S,5S)-3-(2-Bromoethyl)-7-chloro-5-cyclopropylethynyl-1,5-dihydro-5-(trifluoromethyl)-4,1-benzoxazepin-2(3H)-one in 1.5 mL of dry THF and 8 mL of ethanol was added, and the resulting mixture was stirred at ambient temperature for 2 h, at which time an additional 20 for an additional 2 h. The reaction mixture was partitioned between water and ether, and the organic layer was washed with aqueous bicarbonate and brine, dried and evaporated. The crude product was purified by column chromatography over silica gel (elution with 10-25% ethyl acetate in hexanes) to give 130 mg of the title compound as a pure solid: HRMS: Calcd. for C17H14NO2F3Cl (M+H)+: 354.0508. Found: 354.0487.

Workup

  1. stirringthe resulting mixture was stirred at ambient temperature for 2 h, at which time an additional 20 for an additional 2 h
  2. customThe reaction mixture was partitioned between water and ether
  3. washthe organic layer was washed with aqueous bicarbonate and brine
  4. customdried
  5. customevaporated
  6. customThe crude product was purified by column chromatography over silica gel (elution with 10-25% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-2bea407f22e04b39a98215a2aeec43bf
Source dataset
uspto-grants-2002_12
Patent number
US06489320B1

Reaction notes

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