Boron tribromide → 4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenol

HRID 1626088Notes

Reaction equation

HRID 1626088 reaction equation
[F:1][C:2]1([F:22])[CH2:7][O:6][C:5]([NH2:8])=[N:4][C@@:3]1([C:10]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[C:13]([O:19]C)=[CH:12][C:11]=1[F:21])[CH3:9].B(Br)(Br)Br>ClCCl>[NH2:8][C:5]1[O:6][CH2:7][C:2]([F:1])([F:22])[C@:3]([C:10]2[C:11]([F:21])=[CH:12][C:13]([OH:19])=[C:14]([N+:16]([O-:18])=[O:17])[CH:15]=2)([CH3:9])[N:4]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 71008902(R)-5,5-difluoro-4-(2-fluoro-4-methoxy-5-nitro-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine

Product 1

HCID 710088104-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenolYield 56.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of (R)-5,5-difluoro-4-(2-fluoro-4-methoxy-5-nitro-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (intermediate A6.11) (558 mg, 1.75 mmol) in dichloromethane (16 ml) was cooled to 0° C. and treated with a solution of boron tribromide in dichloromethane (1M, 2.62 ml). After stirring at room temperature for 2 hours, the reaction mixture was diluted with dichloromethane, then extracted with water (3 ml). The organic layer was separated, dried over sodium sulphate and evaporated. The crude product was purified by flash chromatography on silica gel using a gradient of hexane/ethyl acetate=100:0 to 0:100 as the eluent. The 4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenol (intermediate F2.1) (300 mg, 56% yield) was obtained as a brown solid. MS (ISP): m/z=457.3 [M+H]+.

Workup

  1. extractionextracted with water (3 ml)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulphate
  4. customevaporated
  5. customThe crude product was purified by flash chromatography on silica gel using a gradient of hexane/ethyl acetate=100:0 to 0:100 as the eluent

Sources & evidence

ORD record
ord-fa3c0f76a9c4446bb3acecd7502f0db8
Source dataset
uspto-grants-2014_07
Patent number
US08785436B2

Reaction notes

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