Sodium Bicarbonate → 8-{2-[2-(4-fluorophenyl)-1,1-dimethylethylamino]-1-hydroxyethyl}-6-hydroxy-4H-benzo[1,4]oxazin-3-one

HRID 12121Notes

Reaction equation

HRID 12121 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]([C:20](=[O:24])[CH:21](O)O)[C:12]2[O:17][CH2:16][C:15](=[O:18])[NH:14][C:13]=2[CH:19]=1)C1C=CC=CC=1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][C:33]([NH2:36])([CH3:35])[CH3:34])=[CH:28][CH:27]=1.[BH4-].[Na+].C(=O)([O-])O.[Na+]>C(O)C>[F:25][C:26]1[CH:27]=[CH:28][C:29]([CH2:32][C:33]([NH:36][CH2:21][CH:20]([C:11]2[C:12]3[O:17][CH2:16][C:15](=[O:18])[NH:14][C:13]=3[CH:19]=[C:9]([OH:8])[CH:10]=2)[OH:24])([CH3:34])[CH3:35])=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 5184711-(4-Fluorophenyl)-2-methyl-2-aminopropaneHCID 4311764Sodium borohydrideHCID 220634476-benzyloxy-8-(2,2-dihydroxyacetyl)-4H-benzo[1,4]oxazin-3-one

Product 1

HCID 115677518-{2-[2-(4-fluorophenyl)-1,1-dimethylethylamino]-1-hydroxyethyl}-6-hydroxy-4H-benzo[1,4]oxazin-3-one

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

300 mg (0.91 mmol) of 6-benzyloxy-8-(2,2-dihydroxyacetyl)-4H-benzo[1,4]oxazin-3-one and 183 mg (1.09 mmol) of 2-(4-fluorophenyl)-1,1-dimethylethylamine were dissolved in 3 mL of ethanol. Molecular sieve was added and the mixture was heated to 80° C. for 30 minutes. After cooling to ambient temperature, 35 mg (0.91 mmol) of sodium borohydride was added. The mixture was stirred for 1 hour at ambient temperature, then sodium hydrogen carbonate solution was added to the reaction mixture and it was extracted with ethyl acetate. The organic phases were evaporated down and the residue was chromatographed (eluent: hexane-ethyl acetate-methanol). The ethanolamine thus obtained (223 mg) was dissolved in methanol to cleave the benzyl protecting group and hydrogenated with 150 mg palladium hydroxide as catalyst at ambient temperature and normal pressure. The catalyst was separated off by filtering through CELITE® filter agent, the filtrate was freed from solvent and the residue was chromatographed (silica gel; eluent: dichloromethane-methanol). Beige solid. Yield: 76 mg (22%); mass spectrometry: [M+H]+=375.

Workup

  1. additionMolecular sieve was added
  2. temperatureAfter cooling to ambient temperature
  3. extractionwas extracted with ethyl acetate
  4. customThe organic phases were evaporated down
  5. customthe residue was chromatographed (eluent: hexane-ethyl acetate-methanol)

Sources & evidence

ORD record
ord-b71c40ec675c45b69826f0b263f21708
Source dataset
uspto-grants-2010_06
Patent number
US07727984B2

Reaction notes

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