Nitric Acid → (4aS,5R,7aS)-2-Amino-7a-(2-fluoro-5-nitrophenyl)-3,5-dimethyl-4a,5,7,7a-tetrahydrofuro[3,4-d]pyrimidin-4(3H)-one

HRID 2281848Notes

Reaction equation

HRID 2281848 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@:8]12[CH2:16][O:15][C@H:14]([CH3:17])[C@H:13]1[C:12](=[O:18])[N:11]([CH3:19])[C:10]([NH:20]C(=O)OC(C)(C)C)=[N:9]2.[OH-].[Na+].[NH4+].[Cl-].[N+:32]([O-])([OH:34])=[O:33]>>[NH2:20][C:10]1[N:11]([CH3:19])[C:12](=[O:18])[C@@H:13]2[C@@H:14]([CH3:17])[O:15][CH2:16][C@:8]2([C:3]2[CH:4]=[C:5]([N+:32]([O-:34])=[O:33])[CH:6]=[CH:7][C:2]=2[F:1])[N:9]=1

Participants

5

Reactant 4

HCID 944Nitric AcidHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 69937526tert-Butyl ((4aS,5R,7aS)-7a-(2-fluorophenyl)-3,5-dimethyl-4-oxo-3,4,4a,5,7,7a-hexahydrofuro[3,4-d]pyrimidin-2-yl)carbamate

Product 1

HCID 66869510(4aS,5R,7aS)-2-Amino-7a-(2-fluoro-5-nitrophenyl)-3,5-dimethyl-4a,5,7,7a-tetrahydrofuro[3,4-d]pyrimidin-4(3H)-one

Procedure

tert-Butyl ((4aS,5R,7aS)-7a-(2-fluorophenyl)-3,5-dimethyl-4-oxo-3,4,4a,5,7,7a-hexahydrofuro[3,4-d]pyrimidin-2-yl)carbamate (2.15 g, 5.7 mmol) was taken up in fuming nitric acid (5 ml) at RT—note exotherm. The dark brown solution was stirred at RT overnight and then at 50° C. for 24 h. The reaction was allowed to cool to RT. Ice (˜25 g) was added and then the mixture was basified with 50% aqueous NaOH with ice bath cooling. The pH was readjusted with saturated aqueous NH4Cl and then the mixture was extracted with DCM (×4). The combined extracts were dried (Na2SO4), filtered and evaporated to give the title compound (1.8 g, yellow foam). LCMS (Method A) Rt 3.00 min; ESI-MS: m/z 323 [M+H]+. This material was used without further manipulation.

Workup

  1. waitat 50° C. for 24 h
  2. temperatureto cool to RT
  3. temperaturecooling
  4. extractionthe mixture was extracted with DCM (×4)
  5. dry with materialThe combined extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-a62c75b67fbd4c4ca8ecd5d0c0940c69
Source dataset
uspto-grants-2015_09
Patent number
US09139594B2

Reaction notes

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