Triphosgene → HCID 53241613, compound

HRID 1023597Notes

Reaction equation

HRID 1023597 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:20])[C@@H:17]([CH3:19])[NH2:18])=[CH:11][CH:10]=2)=[CH:4][C:3]=1[O:21][CH3:22].Cl[C:24](Cl)([O:26]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH3:19][C@H:17]1[NH:18][C:24](=[O:26])[N:15]([C:12]2[CH:13]=[CH:14][C:9]([O:8][C:5]3[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([O:21][CH3:22])[CH:4]=3)=[CH:10][CH:11]=2)[C:16]1=[O:20]

Participants

4

Reactant 2

HCID 94429TriphosgeneHCID 67235119HCID 67235119, compound2×

Product 1

HCID 53241613HCID 53241613, compoundYield 157%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of N1-(4-{[4-methyl-3-(methyloxy)phenyl]oxy}phenyl)-D-alaninamide (Intermediate 22, 215 mg) in dry dichloromethane (15 mL) triethylamine (0.499 mL, 3.58 mmol) was added and the reaction mixture was cooled to 0° C. A solution of triphosgene (96 mg, 0.322 mmol) in dry dichloromethane (5 mL) was slowly added and the reaction mixture was stirred for 30 minutes at the same temperature. The reaction was quenched with water (10 mL) and extracted with dichloromethane (20 mL). The organic layer was dried over sodium sulphate, filtered and evaporated and the residue was purified by flash chromatography (Biotage system, SNAP column) on silica gel using as eluent a gradient cyclohexane/ethyl acetate from 80/20 to 40/60 to afford the title compound as a white solid (165 mg).

Workup

  1. customThe reaction was quenched with water (10 mL)
  2. extractionextracted with dichloromethane (20 mL)
  3. dry with materialThe organic layer was dried over sodium sulphate
  4. filtrationfiltered
  5. customevaporated
  6. customthe residue was purified by flash chromatography (Biotage system, SNAP column) on silica gel using as eluent a gradient cyclohexane/ethyl acetate from 80/20 to 40/60

Sources & evidence

ORD record
ord-b20fbee65e53441dba2ef86f097cb0c5
Source dataset
uspto-grants-2014_05
Patent number
US08722695B2

Reaction notes

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