Benzyl chloroformate → Boc-dap(Z)-OH
Reaction equation
[NH:1]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][NH2:4].C([O-])([O-])=O.[K+].[K+].[OH-].[K+].[CH:23]1[CH:28]=[CH:27][C:26]([CH2:29][O:30][C:31](Cl)=[O:32])=[CH:25][CH:24]=1>O.C1COCC1>[NH:1]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][NH:4][C:31]([O:30][CH2:29][C:26]1[CH:27]=[CH:28][CH:23]=[CH:24][CH:25]=1)=[O:32]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- -5 °C
Procedure
A stirring mixture of the N-Boc-Dap-OH 1 (10.00 g, 49.02 mmol), THF (90 mL), water (30 mL), K2CO3 (13.53 g, 98.04 mmol) and KOH (2.75 g, 49.02 mmol) was cooled to −5° C. Cbz-Cl solution (50 wt % in toluene, 25 mL, 73.53 mmol) was then added dropwise over a period of an hour. The mixture was allowed to stir for 8 h before being concentrated under reduced pressure to remove the THF. The aqueous residue was extracted with diethyl ether (50 mL), acidified to pH 4 by solid citric acid and the resulting precipitate was extracted by CH2Cl2 (2 50 mL). Combined organic layers were dried (Na2SO4) and evaporated to furnish the free acid 2 (15.57 g, 94% yield) as a gummy white solid which was used without further purification. 1H NMR (300 MHz, CDCl3) δ10.76 (1H), 7.25 (5H), 6.24, 5.67 (2H), 5.85 (1H), 5.08, 5.02 (2H), 4.36-4.23 (1H), 3.63-3.35 (2H), 1.38 (9H); 13C NMR (75 MHz, CDCl3)δ 173.5, 157.5, 156.2, 136.4, 128.6, 128.2, 80.6, 67.3, 54.4, 42.9, 28.6.
Workup
- concentrationbefore being concentrated under reduced pressure
- customto remove the THF
- extractionThe aqueous residue was extracted with diethyl ether (50 mL)
- extractionthe resulting precipitate was extracted by CH2Cl2 (2 50 mL)
- dry with materialCombined organic layers were dried (Na2SO4)
- customevaporated
Sources & evidence
- ORD record
- ord-2cb57f19cf16490488ec1898174ca183
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09394338B2
Reaction notes
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