HCID 57827394, compound → (+/-)-[(3R*,4S*)-4-Amino-4-(2-fluorophenyl)tetrahydrofuran-3-yl]methanol

HRID 2281844Notes

Reaction equation

HRID 2281844 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@:8]12[CH2:15][O:14][CH2:13][C@H:12]1[CH2:11][O:10][NH:9]2>C(O)(=O)C.[Zn]>[NH2:9][C@@:8]1([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[CH2:15][O:14][CH2:13][C@H:12]1[CH2:11][OH:10]

Participants

4

Reactant 1

HCID 57827394HCID 57827394, compound

Product 1

HCID 57827606(+/-)-[(3R*,4S*)-4-Amino-4-(2-fluorophenyl)tetrahydrofuran-3-yl]methanolYield 96.6%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Procedure

Zinc (powder, 21 g) was added to a solution containing (±)-(3aS*,6aS*)-6a-(2-fluorophenyl)tetrahydrofuro[3,4-c]isoxazole (5.6 g) in acetic acid (140 mL) at RT. The reaction solution was stirred at RT for 16 h. The insoluble matter was separated by filtration through celite and the filtrate was concentrated under reduced pressure. EtOAc and a sodium bicarbonate solution were added to the residue, and the organic layer was separated. The organic layer was washed with saturated aqueous sodium chloride. The aqueous layer was further extracted with EtOAc three times. The organic layers were combined and dried over anhydrous MgSO4. The insoluble matter was separated by filtration and the filtrate was concentrated under reduced pressure to obtain the title compound (5.46 g). ESI-MS; m/z 212 [M+H]+. 1H NMR (CDCl3) δ ppm 2.81-2.88 (m, 1H), 3.83 (dd, J=6.8, 12.0 Hz, 1H), 3.92 (dd, J=3.2, 8.8 Hz, 1H), 3.94-4.00 (m, 2H), 4.07 (dd, J=8.4, 9.2 Hz, 1H), 4.14 (dd, J=1.2, 8.8 Hz, 1H), 7.09 (ddd, J=1.2, 8.0, 12.4 Hz, 1H), 7.16 (ddd, J=1.2, 7.6, 8.0 Hz, 1H), 7.26-7.32 (m, 1H), 7.53 (dt, J=2.0, 8.0 Hz, 1H).

Workup

  1. customThe insoluble matter was separated by filtration through celite
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. additionEtOAc and a sodium bicarbonate solution were added to the residue
  4. customthe organic layer was separated
  5. washThe organic layer was washed with saturated aqueous sodium chloride
  6. extractionThe aqueous layer was further extracted with EtOAc three times
  7. dry with materialdried over anhydrous MgSO4
  8. customThe insoluble matter was separated by filtration
  9. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-1501936371c548deb71ab2b6b2f714c6
Source dataset
uspto-grants-2015_09
Patent number
US09139594B2

Reaction notes

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