Triphosgene → HCID 71113069, compound

HRID 716830Notes

Reaction equation

[CH2:1]1[C:5]2[CH:6]=[CH:7][C:8]([O:10][C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:22])[C@@H:19]([CH3:21])[NH2:20])=[CH:13][CH:12]=3)=[CH:9][C:4]=2[CH2:3][O:2]1.Cl[C:24](Cl)([O:26]C(=O)OC(Cl)(Cl)Cl)Cl.C([O-])(O)=O.[Na+]>ClCCl>[CH2:1]1[C:5]2[CH:6]=[CH:7][C:8]([O:10][C:11]3[CH:12]=[CH:13][C:14]([N:17]4[C:18](=[O:22])[C@@H:19]([CH3:21])[NH:20][C:24]4=[O:26])=[CH:15][CH:16]=3)=[CH:9][C:4]=2[CH2:3][O:2]1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of N1-[4-(1,3-dihydro-2-benzofuran-5-yloxy)phenyl]-D-alaninamide (Intermediate 77, 100 mg, 0.335 mmol) and TEA (0.234 ml, 1.676 mmol) in dichloromethane (10 ml) was stirred under argon at 0° C. Triphosgene (49.7 mg, 0.168 mmol) in dichloromethane (4 ml) was added and the mixture was left stirring at 0° C. for 15 minutes. After 30 min an aqueous saturated solution of NaHCO3 was added. The phases were separated and the aqueous phase was extracted 3 times with dichloromethane. The gathered organic phases were dried over sodium sulphate and concentrated under vacuum. The residue obtained was purified by flash chromatography (Biotage SP1), using as eluents a gradient cyclohexane/ethyl acetate 90:10 to 65:45 to 20:80. This afforded the title compound (20 mg).

Workup

waitthe mixture was left
customThe phases were separated
extractionthe aqueous phase was extracted 3 times with dichloromethane
dry with materialThe gathered organic phases were dried over sodium sulphate
concentrationconcentrated under vacuum
customThe residue obtained
customwas purified by flash chromatography (Biotage SP1)

Sources & evidence

ORD record: ord-08b19a6c3e8d487294d6d02228569922
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09193704B2

Reaction notes

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