Allyl bromide → N-[(1,1-Dimethylethoxy)carbonyl]-3-fluoro-O-2-propen-1-yl-D-tyrosine
Reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([NH:10][C@H:11]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([F:23])[CH:17]=1)[C:12]([OH:14])=[O:13])=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH2:24](Br)[CH:25]=[CH2:26]>CN(C=O)C>[CH2:26]([O:22][C:19]1[CH:20]=[CH:21][C:16]([CH2:15][C@@H:11]([NH:10][C:8]([O:7][C:3]([CH3:6])([CH3:4])[CH3:5])=[O:9])[C:12]([OH:14])=[O:13])=[CH:17][C:18]=1[F:23])[CH:25]=[CH2:24]Participants
Conditions
- Temperature
- 0 °C
Procedure
1.18 g (60%, 29.39 mmol) of sodium hydride were added to a solution of 4.0 g (13.36 mmol) of (R)-2-tert-butoxycarbonylamino-3-(3-fluoro-4-hydroxyphenyl)propionic acid in 23 ml of DMF while stirring at 0° C., and the mixture was stirred at this temperature. After 15 min, 1.27 ml (1.78 g, 14.7 mmol) of allyl bromide were added, and stirring was continued for 1 h while the mixture reached RT. It was quenched with methanol and, after cooling, excess methanol was removed in a rotary evaporator. Dilution with diethyl ether was followed by acidification with 1N hydrochloric acid, and the aqueous phase was extracted twice more with diethyl ether, and the combined organic phases were washed with saturated sodium chloride solution, dried over NaSO4, filtered and concentrated. 4.50 g of a yellowish oil were obtained.
Workup
- stirringthe mixture was stirred at this temperature
- stirringstirring
- waitwas continued for 1 h while the mixture
- customreached RT
- customIt was quenched with methanol
- temperatureafter cooling
- customexcess methanol was removed in a rotary evaporator
- extractionthe aqueous phase was extracted twice more with diethyl ether
- washthe combined organic phases were washed with saturated sodium chloride solution
- dry with materialdried over NaSO4
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-516daff1b4af466b9620568ff193297e
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09309207B2
Reaction notes
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