HCID 70495472, compound → ((2S,3R,4S)-4-amino-4-(2-fluorophenyl)-2-(trifluoromethyl)tetrahydrofuran-3-yl)methanol

HRID 2195751Notes

Reaction equation

HRID 2195751 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][C@H:13]([C:16]([F:19])([F:18])[F:17])[C@H:12]1[CH2:11][O:10][NH:9]2>C(O)(=O)C.CCOC(C)=O.[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][C@H:13]([C:16]([F:19])([F:17])[F:18])[C@H:12]1[CH2:11][OH:10]

Participants

5

Reactant 1

HCID 70495472HCID 70495472, compound

Product 1

HCID 66869282((2S,3R,4S)-4-amino-4-(2-fluorophenyl)-2-(trifluoromethyl)tetrahydrofuran-3-yl)methanolYield 107.4%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(3aR,4S,6aS)-6a-(2-fluorophenyl)-4-(trifluoromethyl)hexahydrofuro[3,4-c]isoxazole (28.76 g) was dissolved in acetic acid (200 mL) and the solution was cooled to 0° C. Zinc (50 g) was added, and the reaction mixture was allowed to warm and stir at RT for 16 h. The reaction mixture was then diluted with EtOAc (500 mL) and filtered through celite, washing with a further 500 mL of EtOAc. The combined organic portions were evaporated, dissolved in chloroform (200 mL), and ammonia (28% aq., 250 mL) was added slowly. The layers were separated, and the aqueous portion was further extracted with chloroform (2×250 mL). The combined organic extracts were dried over anhydrous MgSO4 and evaporated to afford the title compound (31.12 g) which was used in the subsequent step without further purification. 1H-NMR (400 MHz, CDCl3) δ (ppm): 2.93 (ddd, J=7.7, 4.9, 2.5 Hz, 1H), 3.84 (dd, J=12.4, 4.8 Hz, 1H), 4.05 (dd, J=9.2, 3.2 Hz, 1H), 4.17 (dd, J=12.4, 2.3 Hz, 1H), 4.31 (d, J=9.3 Hz, 1H), 4.72 (quin, J=7.3 Hz, 1H), 7.13 (ddd, J=13.1, 8.8, 1.3 Hz, 1H), 7.22 (td, J=7.6, 1.3 Hz, 1H), 7.31-7.40 (m, 1H), 7.51 (td, J=8.0, 1.6 Hz, 1H)

Workup

  1. temperatureto warm
  2. filtrationfiltered through celite
  3. washwashing with a further 500 mL of EtOAc
  4. customThe combined organic portions were evaporated
  5. dissolutiondissolved in chloroform (200 mL)
  6. additionammonia (28% aq., 250 mL) was added slowly
  7. customThe layers were separated
  8. extractionthe aqueous portion was further extracted with chloroform (2×250 mL)
  9. dry with materialThe combined organic extracts were dried over anhydrous MgSO4
  10. customevaporated

Sources & evidence

ORD record
ord-bb1d4d9ed1cc4b93938dd49c5bdb5452
Source dataset
uspto-grants-2012_12
Patent number
US08338407B2

Reaction notes

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