Triphenylphosphine → Benzyl 4-{(1R,2S)-2-[2-(4-bromo-2,5 difluorophenoxy)ethyl]cyclopropyl}piperidine-1-carboxylate
Reaction equation
[OH:1][CH2:2][CH2:3][C@@H:4]1[CH2:6][C@@H:5]1[CH:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[CH2:9][CH2:8]1.[Br:23][C:24]1[C:29]([F:30])=[CH:28][C:27](O)=[C:26]([F:32])[CH:25]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C(Cl)Cl>[Br:23][C:24]1[C:29]([F:30])=[CH:28][C:27]([O:1][CH2:2][CH2:3][C@@H:4]2[CH2:6][C@@H:5]2[CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[O:14])[CH2:9][CH2:8]2)=[C:26]([F:32])[CH:25]=1Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
Benzyl 4-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl]piperidine-1-carboxylate (2.24 g, 7.38 mmol) in DCM (35 ml) was added 4-bromo-2,5-difluorophenol (1.62 g, 7.75 mmol), 3.93 g of triphenylphosphine (polymer-bound, 3.0 mmol/g) and di-tert-butyl diazene-1,2-dicarboxylate (2.21 g, 9.60 mmol). The reaction mixture was stirred at ambient temperature for 4 hours. The solid was filtered off through celite and the filtrate was concentrated. The residue was purified on Biotage column (50 g SNAP silica gel) using a gradient 0-20% then 20% EtOAc in hexanes to afford the title compound as colorless viscous oil. LC/MS (m/z): 496.2 (M+H)+.
Workup
- filtrationThe solid was filtered off through celite
- concentrationthe filtrate was concentrated
- customThe residue was purified on Biotage column (50 g SNAP silica gel)
Sources & evidence
- ORD record
- ord-254e564d1c0645c1a0ceea57e4d1f669
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08957062B2
Reaction notes
Loading…