Acetic Acid → ((2S,3R,4S)-4-amino-4-(2-fluorophenyl)-2-(trifluoromethyl)tetrahydrofuran-3-yl)methanol

HRID 2045878Notes

Reaction equation

HRID 2045878 reaction equation
O.C(O)(=O)C.[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C:13]12[CH2:20][O:19][CH:18]([C:21]([F:24])([F:23])[F:22])[CH:17]1[CH2:16][O:15][NH:14]2.[NH4+].[OH-]>C1COCC1.[Zn].C(Cl)Cl>[NH2:14][C@@:13]1([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[F:6])[CH2:20][O:19][C@H:18]([C:21]([F:24])([F:22])[F:23])[C@H:17]1[CH2:16][OH:15]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 14923Ammonium HydroxideHCID 60169542HCID 60169542, compound

Product 1

HCID 66869282((2S,3R,4S)-4-amino-4-(2-fluorophenyl)-2-(trifluoromethyl)tetrahydrofuran-3-yl)methanolYield 90.8%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Zinc (389.2 g, 5.95 mol) was placed in a reaction vessel, and water was added (893 mL). Acetic acid (135 mL, 2.38 mol) was added while maintaining the temperature below 10° C. After 15 min, 6a-(2-fluorophenyl)-4-(trifluoromethyl)hexahydrofuro[3,4-c]isoxazole (550.0 g, 1.98 mol) was added as a solution in THF (665 mL). The reaction mixture was stirred over 16 h at rt. Methylene chloride (1.89 L) was added, followed by 28% aq. NH4OH (552 mL) while the temperature was kept below 30° C. The mixture was stirred for 30 min, and then filtered over Celite (80 g) rinsing with methylene chloride (378 mL). The aq. layer was extracted with methylene chloride (1.89 L). The organics were combined, washed with sat. aq. NaCl (1.0 L) and concentrated under vacuum to afford an oil (502 g, 90.6%). The crude residue was used in the following step without additional purification.

Workup

  1. temperaturewhile maintaining the temperature below 10° C
  2. customwas kept below 30° C
  3. stirringThe mixture was stirred for 30 min
  4. filtrationfiltered over Celite (80 g)
  5. washrinsing with methylene chloride (378 mL)
  6. extractionThe aq. layer was extracted with methylene chloride (1.89 L)
  7. washwashed with sat. aq. NaCl (1.0 L)
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-12a5dbe68faa4ac3871b96a8e3e15229
Source dataset
uspto-grants-2013_11
Patent number
US08592408B2

Reaction notes

Loading…