Hydrochloric Acid → methyl (4R)-4-[(8-vinylphenanthridin-6-yl)oxy]-L-prolinate hydrochloride
Reaction equation
[CH:1]([C:3]1[CH:16]=[CH:15][C:14]2[C:5](=[C:6]([O:17][C@H:18]3[CH2:22][N:21](C(OC(C)(C)C)=O)[C@H:20]([C:30]([O:32][CH3:33])=[O:31])[CH2:19]3)[N:7]=[C:8]3[C:13]=2[CH:12]=[CH:11][CH:10]=[CH:9]3)[CH:4]=1)=[CH2:2].[ClH:34]>C(Cl)Cl>[ClH:34].[CH:1]([C:3]1[CH:16]=[CH:15][C:14]2[C:5](=[C:6]([O:17][C@H:18]3[CH2:22][NH:21][C@H:20]([C:30]([O:32][CH3:33])=[O:31])[CH2:19]3)[N:7]=[C:8]3[C:13]=2[CH:12]=[CH:11][CH:10]=[CH:9]3)[CH:4]=1)=[CH2:2]Participants
Procedure
To a solution of the product mixture from Step 4 (100 mg, 0.26 mmol) in DCM (5 mL) was bubbled HCl(g) for 10 min. After stirring for an additional 30 min, the solvent was removed in vacuo to yield methyl (4R)-4-[(8-vinylphenanthridin-6-yl)oxy]-L-prolinate hydrochloride, which was taken up in DCM (5 mL) and linker intermediate B20, (2S)-cyclohexyl({[(2,2-dimethylpent-4-en-1-yl)oxy]carbonyl}amino)acetic acid (85 mg, 0.29 mmol), TEA (0.073 mL, 0.52 mmol), EDC (63 mg, 0.33 mmol), and HOBT (50 mg, 0.33 mmol) were added. The mixture was stirred at r.t. for 18 h, the solvent was removed in vacuo, and the residue was taken up in EtOAc and extracted with NaHCO3. The organic layer was dried over MgSO4 and the solvent was removed in vacuo. The crude material was then purified on silica (gradient elution, 10-50% EtOAc/hex) to yield the title compound as a 1:1 mixture with the expected regioisomer. LRMS (M+H)+=628.4.
Workup
- customthe solvent was removed in vacuo
Sources & evidence
- ORD record
- ord-8d5e063135104ebb8774f6daaa56db47
- Source dataset
- uspto-grants-2015_01
- Patent number
- US08927569B2
Reaction notes
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