Ethyl Acetate → HCID 86600132, compound

HRID 1453992Notes

Reaction equation

HRID 1453992 reaction equation
C(ON=O)(C)(C)C.N[CH:9]1[N:34]([C:35]#[N:36])[CH:12]2[CH:13]([C:23]3[CH:28]=[C:27]([O:29][CH3:30])[C:26]([O:31][CH3:32])=[C:25]([Br:33])[CH:24]=3)[CH:14]=[C:15]3[C:20]([O:19][C:18](=[O:21])[C:17]([CH3:22])=[CH:16]3)=[C:11]2[O:10]1.[BH4-].[Na+].CCOC(C)=O>C1COCC1.ClCCl>[Br:33][C:25]1[CH:24]=[C:23]([CH:13]2[CH:12]3[N:34]([C:35]#[N:36])[CH2:9][O:10][C:11]3=[C:20]3[C:15]([CH:16]=[C:17]([CH3:22])[C:18](=[O:21])[O:19]3)=[CH:14]2)[CH:28]=[C:27]([O:29][CH3:30])[C:26]=1[O:31][CH3:32]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10906Tert-Butyl nitriteHCID 4311764Sodium borohydrideHCID 86600131HCID 86600131, compound

Product 1

HCID 86600132HCID 86600132, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

At 0° C., tert-butylnitrite (62 μL, 0.52 mmol) was added to 2-amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-7-methyl-8-oxo-4H-oxazolo[4,5-h]chromene (20 mg, 0.044 mmol) in dry THF (1 mL) and was stirred at this temperature for 2 h. Sodium borohydride (19.8 mg, 0.52 mmol) was added and the reaction was stirred at 0° C. for 3 h. Reaction was quenched with NH4Cl saturated aqueous solution (1 mL) and the mixture was partitioned between water (2 mL) and EtOAc (5 mL). The aqueous layer was extracted with EtOAc (2×5 mL). The organic layers were combined, washed with saturated NaHCO3 (5 mL), brine (5 mL), dried over Na2SO4, filtered and concentrated to a yellow oil. The product was isolated by flash chromatography using a 12S SiO2 system by Biotage, Inc., Charlottesville, Va., using 1 to 2% EtOAc in dichloromethane to yield 10 mg (85%) of 4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-7-methyl-8-oxo-4H-oxazolo[4,5-h]chromene as a light yellow solid. 1H NMR (Acetone-d6) 7.80 (d, J=1.2 Hz, 1H), 7.13-7.11 (m, 2H), 6.99-6.96 (m, 2H), 5.00 (s, 1H), 3.87 (s, 3H), 3.78 (s, 3H), 3.39 (s, 3H).

Workup

  1. stirringthe reaction was stirred at 0° C. for 3 h
  2. customReaction
  3. customwas quenched with NH4Cl saturated aqueous solution (1 mL)
  4. customthe mixture was partitioned between water (2 mL) and EtOAc (5 mL)
  5. extractionThe aqueous layer was extracted with EtOAc (2×5 mL)
  6. washwashed with saturated NaHCO3 (5 mL), brine (5 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to a yellow oil
  10. customThe product was isolated by flash chromatography

Sources & evidence

ORD record
ord-e71a515e0d194db7ac3012c8fd2728c5
Source dataset
uspto-grants-2009_01
Patent number
US07476741B2

Reaction notes

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