Triethylamine → HCID 53241833, compound

HRID 1023610Notes

Reaction equation

HRID 1023610 reaction equation
[CH3:1][C:2]([C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=2)=[CH:10][CH:9]=1)=[O:6])([CH3:4])[NH2:3].C(N(CC)CC)C.Cl[C:31](Cl)([O:33]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH3:4][C:2]1([CH3:1])[NH:3][C:31](=[O:33])[N:7]([C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=3)=[CH:10][CH:9]=2)[C:5]1=[O:6]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 67235810HCID 67235810, compound2×

Product 1

HCID 53241833HCID 53241833, compoundYield 144%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-methyl-N1-(4-{[3-(methyloxy)phenyl]oxy}phenyl)alaninamide (Intermediate 72, 1.33 g) and triethylamine (3.70 mL, 26.6 mmol) in dry dichloromethane (80 mL) at 0° C. was added dropwise a solution of triphosgene (600 mg, 2.022 mmol) in dry dichloromethane (20 mL) and the reaction mixture was stirred for 30 minutes at the same temperature. The reaction was quenched with a saturated solution of ammonium chloride (100 mL) and two phases were separated. Aqueous layer was extracted with dichloromethane (100 mL) and the two organic phases were collected, dried over sodium sulphate, filtered and evaporated. The residue was purified by silica gel chromatography (Biotage system, 100 g SNAP cartridge) using as eluent a gradient and cyclohexane/ethyl acetate from 80/20 to 40/60 to afford the title compound as a white solid (950 mg).

Workup

  1. customThe reaction was quenched with a saturated solution of ammonium chloride (100 mL) and two phases
  2. customwere separated
  3. extractionAqueous layer was extracted with dichloromethane (100 mL)
  4. customthe two organic phases were collected
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by silica gel chromatography (Biotage system, 100 g SNAP cartridge)

Sources & evidence

ORD record
ord-e0b756dc26334ac7bf79f63667c3cbc6
Source dataset
uspto-grants-2014_05
Patent number
US08722695B2

Reaction notes

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