Ammonium formate → rel-(3S,4S)-4-((S)-1-amino-1-(2-fluorophenyl)ethyl)tetrahydrofuran-3-ol

HRID 2178194Notes

Reaction equation

HRID 2178194 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@:8]1([CH3:16])[C@H:12]2[CH2:13][O:14][CH2:15][C@H:11]2[O:10][NH:9]1.C([O-])=O.[NH4+]>C(O)C.[Pd]>[NH2:9][C@@:8]([C@H:12]1[CH2:13][O:14][CH2:15][C@H:11]1[OH:10])([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[F:1])[CH3:16]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 68158180(3S,3aS,6aS)-rel-3-(2-fluoro-phenyl)-3-methyl-hexahydro-furo[3,4-d]isoxazole

Product 1

HCID 68158183rel-(3S,4S)-4-((S)-1-amino-1-(2-fluorophenyl)ethyl)tetrahydrofuran-3-olYield 52.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A solution of (3S,3aS,6aS)-rel-3-(2-fluoro-phenyl)-3-methyl-hexahydro-furo[3,4-d]isoxazole (16.72 g, 72.9 mmol) in ethanol (300 ml) was treated with ammonium formate (36.8 g, 583 mmol) and palladium (5% on carbon; 7.76 g). The reaction mixture was stirred at room temperature for 18 hours, then filtered and the filtrate evaporated at reduced pressure. The crude product was triturated with diisopropyl ether (50 ml) and filtered. The filtrate was evaporated at reduced pressure and the (3S,4S)-4-[(S)-rel-1-amino-1-(2-fluoro-phenyl)-ethyl]-tetrahydro-furan-3-ol (8.69 g, 48% yield) was obtained as a thick colorless oil. MS (ISP): m/z=226.2 [M+H]+. The solid material obtained after filtration, the rel-(3S,4S)-4-[(S)-1-amino-1-(2-fluoro-phenyl)-ethyl]-tetrahydro-furan-3-ol formate (8.21 g, 42% yield), was treated with a saturated solution of sodium hydrogencarbonate (100 ml) and with dichloromethane (100 ml) and stirred for 1 hour. The aqueous layer was separated and extracted with dichloromethane, then the combined organic layers were dried over sodium sulphate and evaporated. An additional amount of the rel-(3S,4S)-4-[(S)-1-amino-1-(2-fluoro-phenyl)-ethyl]-tetrahydro-furan-3-ol (5.6 g, 31% yield) was obtained as a thick colorless oil. MS (ISP): m/z=226.2 [M+H]+.

Workup

  1. filtrationfiltered
  2. customthe filtrate evaporated at reduced pressure
  3. customThe crude product was triturated with diisopropyl ether (50 ml)
  4. filtrationfiltered
  5. customThe filtrate was evaporated at reduced pressure

Sources & evidence

ORD record
ord-f567df153df94240b25f7f1c90a27db9
Source dataset
uspto-grants-2015_06
Patent number
US09067924B2

Reaction notes

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