Phosphorus oxychloride → [(S)-1-(2-fluoro-4-iodo-phenylcarbamoyl)-2-thiophen-2-yl-ethyl]-carbamic acid tert-butyl ester

HRID 1433770Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[S:15][CH:16]=[CH:17][CH:18]=1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:19][C:20]1[CH:26]=[C:25]([I:27])[CH:24]=[CH:23][C:21]=1[NH2:22].P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([C:10](=[O:12])[NH:22][C:21]1[CH:23]=[CH:24][C:25]([I:27])=[CH:26][C:20]=1[F:19])[CH2:13][C:14]1[S:15][CH:16]=[CH:17][CH:18]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: -10 °C

Procedure

To a solution of (S)-2-tert-butoxycarbonylamino-3-thiophen-2-yl-propionic acid (1.1 g, 4.06 mmol) and 2-fluoro-4-iodoaniline (800 mg, 3.38 mmol) in pyridine (15 mL) at −10° C. was slowly added phosphorus oxychloride (0.35 mL, 3.72 mmol) under an atmosphere of dry nitrogen. The mixture was stirred for 2 hours at −10° C. After removal of the solvent and the excess reagent by rotary evaporator, ice water was added. The mixture was extracted with dichloromethane and the organic layer washed with 1 M aqueous citric acid, brine, saturated aqueous sodium carbonate, brine and dried over sodium sulfate. The solvents were removed to give [(S)-1-(2-fluoro-4-iodo-phenylcarbamoyl)-2-thiophen-2-yl-ethyl]-carbamic acid tert-butyl ester as a yellow viscous oil for use in the next step (1.52 g, 92%).

Workup

customat −10° C.
customAfter removal of the solvent
customthe excess reagent by rotary evaporator, ice water
additionwas added
extractionThe mixture was extracted with dichloromethane
washthe organic layer washed with 1 M aqueous citric acid, brine, saturated aqueous sodium carbonate, brine
dry with materialdried over sodium sulfate
customThe solvents were removed

Sources & evidence

ORD record: ord-e4d8e198d1fc41dba5a00fb46b796a79
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07612212B2

Reaction notes

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