Water → HCID 68628951, compound
Reaction equation
[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1[CH:13]=[C:12]([F:14])[C:11]([F:15])=[CH:10][C:9]=1[CH2:16]Cl)([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.Cl.[CH3:29][O:30][C:31](=[O:34])[CH2:32][NH2:33].O>CN(C=O)C>[CH3:29][O:30][C:31](=[O:34])[CH2:32][NH:33][CH2:16][C:9]1[CH:10]=[C:11]([F:15])[C:12]([F:14])=[CH:13][C:8]=1[NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:18]Participants
Procedure
To a solution of (2-chloromethyl-4,5-difluoro-phenyl)-carbamic acid tert-butyl ester) (5.65 g, 20.3 mmol) in DMF (50 mL) was added DIPEA (10.6 mL, 60.9 mmol). The resulting solution was stirred for 5 min, followed by dropwise addition of solution of glycine methyl ester hydrochloride in DMF at 0° C. The reaction mixture was stirred overnight at 50° C. After completion of the reaction as confirmed by TLC, water (60 mL) was added to the reaction mixture and crude compound was extracted with EtOAc (3×50 mL). The combined organic layers were dried over Na2SO4. The solvents were removed in vacuo to afford the crude compound which was purified by column chromatography (silica gel: 1.5:8.5 EtOAc:Pet. ether) to obtain pure (2-tert-butoxycarbonylamino-4,5 difluoro-benzylamino)-acetic acid methyl ester (5.37 g, 80%) as thick gel.
Workup
- stirringThe reaction mixture was stirred overnight at 50° C
- customAfter completion of the reaction
- additionwas added to the reaction mixture and crude compound
- extractionwas extracted with EtOAc (3×50 mL)
- dry with materialThe combined organic layers were dried over Na2SO4
- customThe solvents were removed in vacuo
- customto afford the crude compound which
- customwas purified by column chromatography (silica gel: 1.5:8.5 EtOAc:Pet. ether)
Sources & evidence
- ORD record
- ord-23163606cd4a4085b0b0278c637b51c6
- Source dataset
- uspto-grants-2013_06
- Patent number
- US08455479B2
Reaction notes
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