HCID 70558534, compound → HCID 70556450, compound

HRID 707717Notes

Reaction equation

HRID 707717 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@:9]12[CH2:16][O:15][C@H:14]([CH2:17][O:18][C:19]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C@H:13]1[CH2:12][O:11][NH:10]2>C(O)(=O)C.[Zn]>[NH2:10][C@@:9]1([C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=2[F:1])[CH2:16][O:15][C@H:14]([CH2:17][O:18][C:19]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C@H:13]1[CH2:12][OH:11]

Participants

4

Reactant 1

HCID 70558534HCID 70558534, compound

Product 1

HCID 70556450HCID 70556450, compound

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Procedure

Zinc powder (10.1 g) was added to a suspension of (3aR,4S,6aS)-6a-(2,3-Difluorophenyl)-4-((trityloxy)methyl)tetrahydrofuro[3,4-c]isoxazole, obtained in Preparation Example 4-(22), (7.76 g) in acetic acid (75 ml) at RT. The mixture was stirred for 11.5 h at RT then the solid was removed by filtration through celite. The filtrate was concentrated in vacuo, then the residue was dissolved with EtOAc. 28% ammonia aqueous solution was added slowly, and the organic layer was separated, washed with brine, and dried over MgSO4. The solid was removed by filtration and the filtrate was concentrated under reduced pressure. Zinc powder (10.1 g) was added to the suspension of the residue in acetic acid (75 ml) at RT. After the mixture was stirred for 11.5 h at same temperature, the solid was removed by filtration through celite. The filtrate was concentrated in vacuo, then the residue was dissolved with EtOAc. 28% ammonia aqueous solution was added slowly, and the organic layer was separated, washed with brine, and dried over MgSO4. The solid was removed by filtration, and the filtrate was concentrated under reduced pressure. The crude mixture was purified by amino silica gel column chromatography (gradient from 50% to 100% EtOAc in heptane) to afford the titled compound (7.04 g) as a white solid. 1H-NMR (400 MHz, CDCl3) δ (ppm): 2.60-2.64 (m, 1H), 3.27 (d, J=4.8 Hz, 2H), 3.61-3.65 (m, 1H), 3.89-3.94 (m, 2H), 4.30 (d, J=9.2 Hz, 1H), 4.33-4.37 (m, 1H), 7.04-7.16 (m, 2H), 7.20-7.30 (m, 10H), 7.40-7.43 (m, 6H)

Workup

  1. customat RT
  2. customthe solid was removed by filtration through celite
  3. concentrationThe filtrate was concentrated in vacuo
  4. dissolutionthe residue was dissolved with EtOAc
  5. addition28% ammonia aqueous solution was added slowly
  6. customthe organic layer was separated
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. customThe solid was removed by filtration
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. additionZinc powder (10.1 g) was added to the suspension of the residue in acetic acid (75 ml) at RT
  12. stirringAfter the mixture was stirred for 11.5 h at same temperature
  13. customthe solid was removed by filtration through celite
  14. concentrationThe filtrate was concentrated in vacuo
  15. dissolutionthe residue was dissolved with EtOAc
  16. addition28% ammonia aqueous solution was added slowly
  17. customthe organic layer was separated
  18. washwashed with brine
  19. dry with materialdried over MgSO4
  20. customThe solid was removed by filtration
  21. concentrationthe filtrate was concentrated under reduced pressure
  22. customThe crude mixture was purified by amino silica gel column chromatography (gradient from 50% to 100% EtOAc in heptane)

Sources & evidence

ORD record
ord-b0b2c262f4ac4a21b27ffffc6d4fa069
Source dataset
uspto-grants-2015_11
Patent number
US09175013B2

Reaction notes

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