Dichloromethane → HCID 69758340, compound

HRID 1359345Notes

Reaction equation

HRID 1359345 reaction equation
ClCCl.[CH2:4]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([N:17]2[CH2:21][C@@H:20](O)[C@H:19]([O:23][CH2:24][O:25][CH3:26])[CH2:18]2)[N:12]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(N(S(F)(F)[F:33])CC)C>O>[CH2:4]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([N:17]2[CH2:21][C@H:20]([F:33])[C@H:19]([O:23][CH2:24][O:25][CH3:26])[CH2:18]2)[N:12]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

5

Reactant 3

HCID 6344Dichloromethane2×HCID 123472(Diethylamino)sulfur trifluorideHCID 69758819HCID 69758819, compound

Product 1

HCID 69758340HCID 69758340, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

5.0 ml of a dichloromethane solution of 2-benzyl-6-[(3R,4R)-3-methoxymethyloxy-4-hydroxypyrrolidine-1-yl]pyridine was added dropwise into a solution of 10 ml of dichloromethane containing 278 μl of diethylaminosulfur trifluoride at −78° C. over 10 minutes. After stirring at room temperature for one hour, it was heated under stirring at 40° C. for one hour. After cooling as it was, the reaction solution was poured into water. The mixture was extracted with ethyl acetate, and the organic phase was washed with brine and the solvent was removed. Then, the residue was subjected to silica gel column chromatography and eluted with hexane/ethyl acetate (10:1) and then with hexane/ethyl acetate (2:1), to give 56.7 mg of 2-benzyl-6-[(3R,4S)-3-methoxymethyloxy-4-fluoropyrrolidine-1-yl]pyridine (1H-NMR (CDCl3) δ=3.38 (3H, s), 3.65-3.82 (4H, m), 3.97 (2H, s), 4.41-4.43 (1H, m), 4.69-4.75 (2H, m), 5.18 (1H, br.d, J=49 Hz), 6.18 (1H, d, J=8 Hz), 6.38 (1H, d, J=7 Hz), 7.01-7.36 (6H, m)) and 294 mg of a crude refined product of 2-benzyl-6-[(3R,4S)-3-(fluoromethoxy)-4-methoxypyrrolidine-1-yl]pyridine. This crude purified product was purified by a thin layer chromatography (developed three timed using hexane/ethyl acetate (5/1) and three times using hexane/ethyl acetate (4/1)), to give 47.8 g of 2-benzyl-6-[(3R,4S)-3-(fluoromethoxy)-4-methoxypyrrolidine-1-yl]pyridine (1H-NMR (CDCl3) δ=3.48 (3H, s), 3.54-3.73 (4H, m), 3.97 (2H, s), 4.00-4.04 (1H, m), 4.41-4.46 (1H, m), 5.41 (2H, d, J=56 Hz), 6.15 (1H, d, J=8 Hz), 6.37 (1H, d, J=7 Hz), 7.17-7.35 (6H, m)).

Workup

  1. temperatureit was heated
  2. stirringunder stirring at 40° C. for one hour
  3. temperatureAfter cooling as it
  4. extractionThe mixture was extracted with ethyl acetate
  5. washthe organic phase was washed with brine
  6. customthe solvent was removed
  7. washeluted with hexane/ethyl acetate (10:1)

Sources & evidence

ORD record
ord-fe066a666ae6429caa2ddbbc9963e485
Source dataset
uspto-grants-2003_07
Patent number
US06599917B1

Reaction notes

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