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

HRID 2178195Notes

Reaction equation

HRID 2178195 reaction equation
C([O:3][C@H:4]1[C@@H:8]([C@:9]([NH2:18])([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])[CH3:10])[CH2:7][O:6][CH2:5]1)=O.C(=O)([O-])O.[Na+]>ClCCl>[NH2:18][C@@:9]([C@H:8]1[CH2:7][O:6][CH2:5][C@H:4]1[OH:3])([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[F:17])[CH3:10]

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 88876294rel-(3S,4S)-4-[(S)-1-amino-1-(2-fluoro-phenyl)-ethyl]-tetrahydro-furan-3-ol formate

Product 1

HCID 68158183rel-(3S,4S)-4-((S)-1-amino-1-(2-fluorophenyl)ethyl)tetrahydrofuran-3-olYield 76.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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. customThe solid material obtained
  2. filtrationafter filtration
  3. customThe aqueous layer was separated
  4. extractionextracted with dichloromethane
  5. dry with materialthe combined organic layers were dried over sodium sulphate
  6. customevaporated

Sources & evidence

ORD record
ord-b728f11dc937473f83d1bb1b65b59cc3
Source dataset
uspto-grants-2015_06
Patent number
US09067924B2

Reaction notes

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