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

HRID 1296080Notes

Reaction equation

HRID 1296080 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:30]=[C:31]([F:33])[CH:32]=1)[CH2:5][C@H:6]([NH:22][C:23](=O)[O:24]C(C)(C)C)[C@H:7]([OH:21])[CH2:8][NH:9][CH:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([I:20])[CH:18]=2)[O:13][CH2:12][CH2:11]1.[CH3:34]CN(CC)CC.C(C1NC=CN=1)(=O)C>C(O)(C(F)(F)F)=O.C(Cl)Cl.C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:30]=[C:31]([F:33])[CH:32]=1)[CH2:5][C@H:6]([NH:22][C:23](=[O:24])[CH3:34])[C@H:7]([OH:21])[CH2:8][NH:9][CH:10]1[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 3

HCID 8471TriethylamineHCID 5389722-AcetylimidazoleHCID 10325781Tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(6-iodo-3,4-dihydro-2H-chromen-4-yl)amino]propylcarbamate

Product 1

HCID 10052240N-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(6-iodo-3,4-dihydro-2H-chromen-4-yl)amino]propyl}acetamideYield 93.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

Tert-butyl (1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(6-iodo-3,4-dihydro-2H-chromen-4-yl)amino]propylcarbamate (3.0 g, 5.2 mmol) was dissolved in 30 mL of 25% TFA/CH2Cl2 and stirred at room temperature for 30 min. The mixture was diluted with CH2Cl2 50 mL and washed with NaHCO3 (2×30 mL). The organic layer was washed with brine (1×50 mL) and dried over Na2SO4. The solvent was removed in vacuo and the resulting residue dissolved in 52 mL of CH2Cl2. The mixture was chilled to 0° C. followed by the addition of Et3N (1.0 mL, 11.9 mmol) and acetyl imidazole (0.68 g, 6.2 mmol). The mixture was warm spontaneously over night. The CH2Cl2 was removed in vacuo and the residue dissolved in EtOAc (100 mL) and washed with 1N HCl (2×30 mL), NaHCO3 (1×30 mL), brine, dried over Na2SO4, and conc. in vacuo to yield 2.5 g (92%) of the title compound as a light yellow solid. MS (ESI+) for C21H23F2IN2O3 m/z 517.0 (M+H)+.

Workup

  1. washwashed with NaHCO3 (2×30 mL)
  2. washThe organic layer was washed with brine (1×50 mL)
  3. dry with materialdried over Na2SO4
  4. customThe solvent was removed in vacuo
  5. dissolutionthe resulting residue dissolved in 52 mL of CH2Cl2
  6. temperatureThe mixture was chilled to 0° C.
  7. temperatureThe mixture was warm spontaneously over night
  8. customThe CH2Cl2 was removed in vacuo
  9. dissolutionthe residue dissolved in EtOAc (100 mL)
  10. washwashed with 1N HCl (2×30 mL), NaHCO3 (1×30 mL), brine
  11. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-6030e9d8e46e4e408d5b15b15d42e428
Source dataset
uspto-grants-2007_07
Patent number
US07244725B2

Reaction notes

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