Ammonium formate → ((2S,3R,4S)-4-Amino-4-(2,4-difluorophenyl)-2-((trityloxy)methyl)tetrahydrofuran-3-yl)methanol

HRID 68372Notes

Reaction equation

HRID 68372 reaction equation
[NH2:1][C@@:2]1([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[C:32](Cl)[C:31]=2[F:38])[CH2:6][O:5][C@H:4]([CH2:7][O:8][C:9]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C@H:3]1[CH2:28][OH:29].C([O-])=O.[NH4+]>[Pd].CO>[NH2:1][C@@:2]1([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=2[F:38])[CH2:6][O:5][C@H:4]([CH2:7][O:8][C:9]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[C@H:3]1[CH2:28][OH:29]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 86707811((2S,3R,4S)-4-Amino-4-(3-chloro-2,4-difluorophenyl)-2-((trityloxy)methyl)tetrahydrofuran-3-yl)methanol

Product 1

HCID 86707812((2S,3R,4S)-4-Amino-4-(2,4-difluorophenyl)-2-((trityloxy)methyl)tetrahydrofuran-3-yl)methanolYield 99.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of ((2S,3R,4S)-4-amino-4-(3-chloro-2,4-difluorophenyl)-2-((trityloxy)methyl)tetrahydrofuran-3-yl)methanol (4.49 g, 8.4 mmol), ammonium formate (3.2 g, 50 mmol) and 10% palladium on carbon (500 mg) in dry MeOH (40 mL) was stirred at RT under nitrogen overnight. The catalyst was removed by filtration through Celite®—washing with methanol. The filtrate was evaporated and the residue was partitioned between DCM (100 mL) and saturated aqueous NaHCO3 (50 mL). The layers were separated and the aqueous layer was further extracted with DCM (100 mL×4). The combined extracts were dried (Na2SO4), filtered and evaporated to give the title compound (4.18 g). 1H NMR (400 MHz, MeOH-d4) δ ppm: 2.73-2.84 (m, 1 H) 3.17 (dd, J=10.03, 5.14 Hz, 1 H) 3.27 (dd, J=9.96, 3.61 Hz, 1 H) 3.65-3.79 (m, 2 H) 3.88 (dd, J=8.93, 3.06 Hz, 1 H) 4.16-4.24 (m, 1 H) 4.27 (d, J=9.05 Hz, 1 H) 6.88-7.00 (m, 2 H) 7.18-7.31 (m, 9 H) 7.38-7.45 (m, 6 H) 7.58-7.67 (m, 1 H).

Workup

  1. customThe catalyst was removed by filtration through Celite®—washing with methanol
  2. customThe filtrate was evaporated
  3. customthe residue was partitioned between DCM (100 mL) and saturated aqueous NaHCO3 (50 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer was further extracted with DCM (100 mL×4)
  6. dry with materialThe combined extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-86562488654041a6b254a048b24267f5
Source dataset
uspto-grants-2014_09
Patent number
US08822455B2

Reaction notes

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