(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid → (2S,4R)-1-(tert-butoxycarbonyl)-4-(phenanthridin-6-yloxy)pyrrolidine-2-carboxylic acid
Reaction equation
[C:1]([N:8]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl[C:18]1[N:19]=[C:20]2[C:25](=[C:26]3[C:31]=1[CH:30]=[CH:29][CH:28]=[CH:27]3)[CH:24]=[CH:23][CH:22]=[CH:21]2.CC(C)([O-])C.[Na+]>CN1C(=O)CCC1>[C:4]([O:3][C:1]([N:8]1[CH2:15][C@H:14]([O:16][C:18]2[N:19]=[C:20]3[C:25](=[C:26]4[C:31]=2[CH:30]=[CH:29][CH:28]=[CH:27]4)[CH:24]=[CH:23][CH:22]=[CH:21]3)[CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])=[O:2])([CH3:7])([CH3:6])[CH3:5]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
(2S,4R)—N-Boc-4-hydroxyproline can be reacted with 6-chlorophenanthridine in NMP, in the presence of sodium t-butoxide, to produce (2S,4R)-1-(tert-butoxycarbonyl)-4-(phenanthridin-6-yloxy)pyrrolidine-2-carboxylic acid. Methyl tertiary butyl ether (MTBE) and water can then be added. The aqueous layer is separated, washed, and then HCl is added, followed by extraction with MTBE. The extracted product can be mixed with diisopropylethylamine (DIPEA) and HATU (CAS #148893-10-1), and then reacted with (1R,2S)-ethyl-1-amino-2-vinylcyclopropanecarboxylate tosylate salt in dimethylformide (DMF) and toluene. The reaction produces (2S,4R)-tert-butyl 2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-(phenanthridin-6-yloxy)pyrrolidine-1-carboxylate, which can be extracted with MTBE and washed with HCl, further extracted, washed, dried, and dissolved in 2-propanol.
Sources & evidence
- ORD record
- ord-d7a0ea3c05514520b1e1dbf55b32ef4e
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09309279B2
Reaction notes
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