(3aR,4S,6aS)-6a-(3-chloro-2,4-difluorophenyl)-4-((trityloxy)methyl)hexahydrofuro[3,4-c]isoxazole → ((2S,3R,4S)-4-Amino-4-(3-chloro-2,4-difluorophenyl)-2-((trityloxy)methyl)tetrahydrofuran-3-yl)methanol

HRID 68371Notes

Reaction equation

HRID 68371 reaction equation
[Cl:1][C:2]1[C:3]([F:38])=[C:4]([C@:9]23[CH2:16][O:15][C@H:14]([CH2:17][O:18][C:19]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C@H:13]2[CH2:12][O:11][NH:10]3)[CH:5]=[CH:6][C:7]=1[F:8]>C(O)(=O)C.[Zn]>[NH2:10][C@@:9]1([C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[C:3]=2[F:38])[CH2:16][O:15][C@H:14]([CH2:17][O:18][C:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C@H:13]1[CH2:12][OH:11]

Participants

4

Reactant 1

HCID 86707810(3aR,4S,6aS)-6a-(3-chloro-2,4-difluorophenyl)-4-((trityloxy)methyl)hexahydrofuro[3,4-c]isoxazole

Product 1

HCID 86707811((2S,3R,4S)-4-Amino-4-(3-chloro-2,4-difluorophenyl)-2-((trityloxy)methyl)tetrahydrofuran-3-yl)methanolYield 96.9%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Procedure

Zinc (2.75 g, 42.1 mmol) was added in one portion to a stirred suspension of (3aR,4S,6aS)-6a-(3-chloro-2,4-difluorophenyl)-4-((trityloxy)methyl)hexahydrofuro[3,4-c]isoxazole (4.5 g, 8.43 mmol) in acetic acid (15 mL) at RT. An exotherm was noted. The mixture was stirred at RT overnight. The zinc was removed by filtration through Celite® washing with methanol. The filtrate was evaporated and the residue was partitioned between DCM and saturated aqueous NaHCO3. The mixture was filtered through Celite® again—washing with DCM and water. The layers were separated and the aqueous layer was further extracted with DCM (×3). The combined extracts were dried by passing through a hydrophobic frit and evaporated to give the title compound (4.38 g). 1H NMR (400 MHz, CDCl3) δ ppm: 2.61-2.71 (m, 1 H) 3.23-3.32 (m, 2 H) 3.68 (dd, J=12.04, 5.32 Hz, 1 H) 3.91 (dd, J=12.10, 4.28 Hz, 1 H) 3.96 (dd, J=9.23, 2.63 Hz, 1 H) 4.28-4.37 (m, 2 H) 6.94-7.01 (m, 1 H) 7.20-7.34 (m, 9 H) 7.38-7.53 (m, 7 H.

Workup

  1. customThe zinc was removed by filtration through Celite®
  2. washwashing with methanol
  3. customThe filtrate was evaporated
  4. customthe residue was partitioned between DCM and saturated aqueous NaHCO3
  5. filtrationThe mixture was filtered through Celite®
  6. washagain—washing with DCM and water
  7. customThe layers were separated
  8. extractionthe aqueous layer was further extracted with DCM (×3)
  9. customThe combined extracts were dried
  10. customevaporated

Sources & evidence

ORD record
ord-7ccc4e08afc24195b9948b8bdb365599
Source dataset
uspto-grants-2014_09
Patent number
US08822455B2

Reaction notes

Loading…