3-Chloropropylamine → (2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-[(benzyloxy)methyl]-1-(3-chloropropyl)piperidine

HRID 1747019Notes

Reaction equation

HRID 1747019 reaction equation
[CH2:1]([O:8][C@H:9]([C@@H:12]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C@H:13]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:14](=O)[CH2:15][O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:10]=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:41][CH2:42][CH2:43][CH2:44][NH2:45].[BH3-]C#N.[Na+]>CO>[CH2:26]([O:25][C@H:13]1[C@H:12]([O:33][CH2:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[C@@H:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:10][N:45]([CH2:44][CH2:43][CH2:42][Cl:41])[C@@H:14]1[CH2:15][O:16][CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

5

Reactant 3

HCID 846293-ChloropropylamineHCID 5003444Sodium cyanoborohydrideHCID 11103493(2R,3R,4S)-2,3,4,6-tetrakis(benzyloxy)-5-oxohexanal

Product 1

HCID 118407745(2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-[(benzyloxy)methyl]-1-(3-chloropropyl)piperidineYield 36%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred suspension of crude (2R,3R,4S)-2,3,4,6-tetrakis(benzyloxy)-5-oxohexanal 3 (20 g, 37.13 mmol) in MeOH (400 mL) were added 3-chloro propylamine (47 g, 743 mmol) at 0° C. and activated molecular sieves (100 g) and the reaction mixture was stirred at room temperature for 20 min. Then the reaction mixture was cooled to 0° C. and solid NaBH3CN (9.33 g, 148.5 mmol) was added to the reaction mixture and stirred at same temperature for 1 h. Then the reaction mixture was stirred at room temperature for 20 h. After removal of the molecular sieves through celite pad, the filtrate was concentrated under reduced pressure. The crude mass was dissolved in ethyl acetate (250 mL) and organic part was washed with saturated solution of NaHCO3 (100 mL), dried over Na2SO4 and concentrated under reduced pressure to get crude which was purified by column chromatography using 100-200 mesh silica gel and eluting with 8% EtOAc/hexane to afford (2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-[(benzyloxy)methyl]-1-(3-chloropropyl)piperidine 4 (8.0 g, 36%) as white solid.

Workup

  1. temperatureThen the reaction mixture was cooled to 0° C.
  2. stirringstirred at same temperature for 1 h
  3. stirringThen the reaction mixture was stirred at room temperature for 20 h
  4. customAfter removal of the molecular sieves through celite pad
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. dissolutionThe crude mass was dissolved in ethyl acetate (250 mL)
  7. washorganic part was washed with saturated solution of NaHCO3 (100 mL)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customto get crude which
  11. customwas purified by column chromatography
  12. washeluting with 8% EtOAc/hexane

Sources & evidence

ORD record
ord-a32efdb2fc084654b6b1190c59f11486
Source dataset
uspto-grants-2015_10
Patent number
US09150557B1

Reaction notes

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