HCID 70558999, compound → HCID 70558117, compound

HRID 707693Notes

Reaction equation

HRID 707693 reaction equation
[F:1][CH2:2][C@@H:3]1[C@@H:10]2[C@@:6]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[F:17])([NH:7][O:8][CH2:9]2)[CH2:5][O:4]1>C(O)(=O)C.[Zn]>[NH2:7][C@@:6]1([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])[CH2:5][O:4][C@H:3]([CH2:2][F:1])[C@H:10]1[CH2:9][OH:8]

Participants

4

Reactant 1

HCID 70558999HCID 70558999, compound

Product 1

HCID 70558117HCID 70558117, compoundYield 100.7%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
0 °C

Procedure

(3aR,4S,6aS)-4-(fluoromethyl)-6a-(2-fluorophenyl)hexahydrofuro[3,4-c]isoxazole (62.20 g, 257.14 mmol) was dissolved in acetic acid (540 mL) and the solution was cooled to 0° C. Zinc dust (168.14 g, 2571.4 mmol) was added over 15 mins. The reaction temperature rose from 8° C. to 16° C. The ice bath was removed after addition and the reaction mixture was allowed to warm up to RT. Internal temperature increased to 40° C. and gradually went down to 24° C. The reaction was stirred at RT for 16 h. The reaction mixture was filtered through celite, and washed with 1.5 L of EtOAc. The solvent was evaporated and the crude product was dissolved in chloroform (600 mL), and ammonia (28% aq., 240 mL) was added slowly using a dropping funnel. Internal temperature rose to 40° C. The layers were separated, and the aqueous layer was further extracted with chloroform (3×250 mL). The combined organic extracts were dried over anhydrous MgSO4 and evaporated to afford the title compound (63.00 g, 100%) which was used in the subsequent step without further purification. 1H-NMR (400 MHz, CDCl3) δ ppm 2.39-2.86 (m, 4H) 3.81 (dd, J=11.87, 4.55 Hz, 1H) 3.94 (dd, J=9.09, 3.03 Hz, 1H) 4.07 (dd, J=12.13, 4.04 Hz, 1H) 4.25 (d, J=9.09 Hz, 1H) 4.40-4.68 (m, 3H) 7.09 (ddd, J=12.57, 8.15, 1.26 Hz, 1H) 7.17 (td, J=7.58, 1.26 Hz, 1H) 7.28-7.34 (m, 1H) 7.49 (td, J=8.08, 1.77 Hz, 1H)

Workup

  1. customrose from 8° C. to 16° C
  2. customThe ice bath was removed
  3. additionafter addition
  4. temperatureto warm up to RT
  5. temperatureInternal temperature increased to 40° C.
  6. customgradually went down to 24° C
  7. filtrationThe reaction mixture was filtered through celite
  8. washwashed with 1.5 L of EtOAc
  9. customThe solvent was evaporated
  10. dissolutionthe crude product was dissolved in chloroform (600 mL)
  11. additionammonia (28% aq., 240 mL) was added slowly
  12. customrose to 40° C
  13. customThe layers were separated
  14. extractionthe aqueous layer was further extracted with chloroform (3×250 mL)
  15. dry with materialThe combined organic extracts were dried over anhydrous MgSO4
  16. customevaporated

Sources & evidence

ORD record
ord-fbb56a56d213484398cf1b448a2ff8c6
Source dataset
uspto-grants-2015_11
Patent number
US09175013B2

Reaction notes

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