Triphosgene → Diisopropylethylamine
Reaction equation
ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.ClC1C=C([C@@H:20]2[C@@H:25]([C:26]3C=CC(Cl)=CC=3)[N:24]([CH:33]([CH2:36]C)[CH2:34]C)[C:23](=O)[C@:22](CC(NN)=O)(C)C2)C=CC=1>C(Cl)Cl>[CH:25]([N:24]([CH:33]([CH3:36])[CH3:34])[CH2:23][CH3:22])([CH3:26])[CH3:20]Participants
Procedure
A solution of 56 mg (0.19 mmol) of triphosgene in DCM (1 mL) was added dropwise to a solution of 62 mg (0.13 mmol) of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)acetohydrazide (obtained as a byproduct in Example 76, Step B) and 170 μL (0.98 mmol) of diisopropylethylamine in DCM (4 mL). The resulting light yellow solution was stirred at room temperature for 18 h, then was quenched with saturated aqueous sodium bicarbonate and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by reversed phase preparative HPLC (Sunfire™ Prep C18 OBD 10 μm column, (Waters, Milford, Mass.) gradient elution of 40% MeCN in water to 75% MeCN in water over a 30 min period, where both solvents contain 0.1% TFA) provided the title compound as a white solid.
Sources & evidence
- ORD record
- ord-891177591c854a79a5c4a3e5b0cac1ea
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09296736B2
Reaction notes
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