Triethylamine → N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(6-iodo-4-methyl-3,4-dihydro-2H-chromen-4-yl)amino]propyl}acetamide

HRID 1296097Notes

Reaction equation

HRID 1296097 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:31]=[C:32]([F:34])[CH:33]=1)[CH2:5][C@H:6]([NH:23][C:24](=[O:30])OC(C)(C)C)[C@H:7]([OH:22])[CH2:8][NH:9][C:10]1([CH3:21])[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([I:20])[CH:18]=2)[O:13][CH2:12][CH2:11]1.[C:35](O)(C(F)(F)F)=O.C(Cl)Cl.CCN(CC)CC.C(C1NC=CN=1)(=O)C>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:31]=[C:32]([F:34])[CH:33]=1)[CH2:5][C@H:6]([NH:23][C:24](=[O:30])[CH3:35])[C@H:7]([OH:22])[CH2:8][NH:9][C:10]1([CH3:21])[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([I:20])[CH:18]=2)[O:13][CH2:12][CH2:11]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5389722-AcetylimidazoleHCID 21863450Trifluoroacetic acid methylene chlorideHCID 86601304tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(6-iodo-4-methyl-3,4-dihydro-2H-chromen-4-yl)amino]propylcarbamate

Product 1

HCID 60206838N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(6-iodo-4-methyl-3,4-dihydro-2H-chromen-4-yl)amino]propyl}acetamideYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a CH2Cl2 (5 ml) solution of tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(6-iodo-4-methyl-3,4-dihydro-2H-chromen-4-yl)amino]propylcarbamate (Diastereomer B). (0.47 g, 0.79 mmol), at r.t., was added 25 ml of 20% TFA/CH2Cl2. The mixture was stirred at r.t for 30 min. The solvent was removed in vacuo and the residue dissolved in CH2Cl2 (75 ml) and washed with aqueous NaHCO3 and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo to yield a white foam. The residue was dissolved in CH2Cl2 (5 ml) and chilled to 0° C. followed by the addition of Et3N (0.24 ml, 1.7 mmol) and acetyl imidazole (0.10 g, 0.90 mmol). The mixture was then warmed to r.t. and stirred overnight. The reaction mixture was diluted with CH2Cl2 (25 ml) and washed with water and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo to yield a white foam (0.35 g, 84%) after flash chromatograph 5% MeOH/CHCl3 (Biotage 40 S). Rf=0.29. HRMS (ESI+) calcd for C22H25N2O3IF2+1H calcd m/z 531.0958; found 531.0958 (M+H)+.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue dissolved in CH2Cl2 (75 ml)
  3. washwashed with aqueous NaHCO3 and brine
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customto yield a white foam
  7. temperatureThe mixture was then warmed to r.t.
  8. stirringstirred overnight
  9. washwashed with water and brine
  10. dry with materialThe organic layer was dried over Na2SO4
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3361f59d32d846cb93e48d8f5d3b2458
Source dataset
uspto-grants-2007_07
Patent number
US07244725B2

Reaction notes

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