Triphosgene → (5R)-5-(1-methylethyl)-3-(4-{[4-methyl-3-(methyloxy)phenyl]oxy}phenyl)-2,4-imidazolidinedione
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:22])[C@@H:17]([CH:19]([CH3:21])[CH3:20])[NH2:18])=[CH:11][CH:10]=2)=[CH:4][C:3]=1[O:23][CH3:24].Cl[C:26](Cl)([O:28]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH3:20][CH:19]([C@H:17]1[NH:18][C:26](=[O:28])[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:23][CH3:24])[CH:4]=3)=[CH:10][CH:11]=2)[C:16]1=[O:22])[CH3:21]Participants
Conditions
- Temperature
- 0 °C
Procedure
To a solution of N1-(4-{[4-methyl-3-(methyloxy)phenyl]oxy}phenyl)-D-valinamide (Intermediate 83, 65 mg) in dry dichloromethane (10 mL), TEA (0.138 mL, 0.990 mmol) was added and the reaction mixture was cooled to 0° C. A solution of triphosgene (26.4 mg, 0.089 mmol) in dry dichloromethane (3 mL) was slowly added and the reaction mixture was stirred for 1 hour at 0° C. The reaction was quenched with water (2 mL) and a saturated aqueous solution of ammonium chloride (5 mL) and was extracted with dichloromethane (2 times 10 mL). The organic layer was dried over sodium sulphate, filtered and evaporated and the residue was purified by silica gel flash chromatography (Biotage system, 10 g SNAP column) using as eluent a gradient cyclohexane/ethyl from 100/0 to 60/40 to afford the title compound as a white solid (55 mg).
Workup
- customThe reaction was quenched with water (2 mL)
- extractiona saturated aqueous solution of ammonium chloride (5 mL) and was extracted with dichloromethane (2 times 10 mL)
- dry with materialThe organic layer was dried over sodium sulphate
- filtrationfiltered
- customevaporated
- customthe residue was purified by silica gel flash chromatography (Biotage system, 10 g SNAP column)
Sources & evidence
- ORD record
- ord-8ad9e2d6d4ac4f11bace3c6da9008b33
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08722695B2
Reaction notes
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