Acetic Acid → ((2R*,3R*,4S*)-4-Amino-4-(2,4-difluorophenyl)-2-methyltetrahydrofuran-3-yl)methanol

HRID 68382Notes

Reaction equation

HRID 68382 reaction equation
Br[C:2]1[C:3]([F:18])=[CH:4][C:5]([F:17])=[C:6]([C@:8]23[CH2:15][O:14][C@H:13]([CH3:16])[C@H:12]2[CH2:11][O:10][NH:9]3)[CH:7]=1.C(O)(=O)C>C1COCC1.[Zn]>[NH2:9][C@@:8]1([C:6]2[CH:7]=[CH:2][C:3]([F:18])=[CH:4][C:5]=2[F:17])[CH2:15][O:14][C@H:13]([CH3:16])[C@H:12]1[CH2:11][OH:10]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 86707821HCID 86707821, compound

Product 1

HCID 68296354((2R*,3R*,4S*)-4-Amino-4-(2,4-difluorophenyl)-2-methyltetrahydrofuran-3-yl)methanolYield 79.6%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Procedure

(3aR*,4R*,6aS*)-6a-(5-Bromo-2,4-difluorophenyl)-4-methylhexahydro furo[3,4-c]isoxazole (200 mg, 0.62 mmol) was dissolved in THF (10 mL). Zinc dust (0.49 g, 7.50 mmol) was added, followed by acetic acid (143 μl, 2.50 mmol) and the reaction was stirred at room temperature overnight. The reaction was filtered through Celite®, washing with MeOH and the filtrate was concentrated in vacuo. The residue was basified with saturated NaHCO3 and DCM added. The mixture was filtered and the layers separated. The aqueous layer was extracted with DCM (×2) and the combined organics were dried (MgSO4) and concentrated to leave the title compound (120 mg).

Workup

  1. filtrationThe reaction was filtered through Celite®
  2. washwashing with MeOH
  3. concentrationthe filtrate was concentrated in vacuo
  4. additionadded
  5. filtrationThe mixture was filtered
  6. customthe layers separated
  7. extractionThe aqueous layer was extracted with DCM (×2)
  8. dry with materialthe combined organics were dried (MgSO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-79f4d6f99ede4d78973cb78ea699cbbd
Source dataset
uspto-grants-2014_09
Patent number
US08822455B2

Reaction notes

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