Triphosgene → HCID 57410333, compound
Reaction equation
[NH2:1][C@H:2]([CH2:24][CH3:25])[C:3]([NH:5][C:6]1[CH:7]=[N:8][C:9]([O:12][C:13]2[C:18]3[C:19]4([CH2:22][O:23][C:17]=3[CH:16]=[CH:15][CH:14]=2)[CH2:21][CH2:20]4)=[CH:10][CH:11]=1)=[O:4].Cl[C:27](Cl)([O:29]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH2:24]([C@H:2]1[NH:1][C:27](=[O:29])[N:5]([C:6]2[CH:7]=[N:8][C:9]([O:12][C:13]3[C:18]4[C:19]5([CH2:22][O:23][C:17]=4[CH:16]=[CH:15][CH:14]=3)[CH2:21][CH2:20]5)=[CH:10][CH:11]=2)[C:3]1=[O:4])[CH3:25]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a solution of (2R)-2-amino-N-[6-(spiro[1-benzofuran-3,1′-cyclopropan]-4-yloxy)-3-pyridinyl]butanamide (Reference Intermediate 218, 90 mg) in dry dichloromethane (15 ml) TEA (0.185 ml, 1.326 mmol) was added and the reaction mixture was cooled to 0° C. A solution of triphosgene (35.4 mg, 0.119 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 two phases were separated. The organic layer was dried over sodium sulphate, filtered and evaporated. The residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane/ethyl acetate 8:2 to cyclohexane/ethyl acetate 1:1 as eluents affording the title compound (65 mg, 0.178 mmol) as a white solid.
Workup
- customThe reaction was quenched with water (10 ml) and two phases
- customwere separated
- dry with materialThe organic layer was dried over sodium sulphate
- filtrationfiltered
- customevaporated
- customThe residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane/ethyl acetate 8:2 to cyclohexane/ethyl acetate 1:1 as eluents
Sources & evidence
- ORD record
- ord-526b9d021ced4ac2afa927d83ad83280
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08722695B2
Reaction notes
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