3-Chlorophenol → tert-Butyl (2S)-2-[(3-chlorophenoxy)methyl]pyrrolidine-1-carboxylate
Reaction equation
N(C(OC(C)C)=O)=NC(OC(C)C)=O.C1COCC1.[CH3:20][C:21]([O:24][C:25]([N:27]1[C@H:31]([CH2:32][OH:33])[CH2:30][CH2:29][CH2:28]1)=[O:26])([CH3:23])[CH3:22].[Cl:34][C:35]1[CH:36]=[C:37](O)[CH:38]=[CH:39][CH:40]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>>[Cl:34][C:35]1[CH:40]=[C:39]([CH:38]=[CH:37][CH:36]=1)[O:33][CH2:32][C@@H:31]1[CH2:30][CH2:29][CH2:28][N:27]1[C:25]([O:24][C:21]([CH3:20])([CH3:22])[CH3:23])=[O:26]Participants
6
Procedure
A solution of diisopropyl azodicarboxylate (1.4 mL, 7.1 mmol) in THF (3.5 mL, 44 mmol) was slowly added to a 0° C. solution of BOC-PRO-OL (1.0 g, 5.0 mmol), 3-chlorophenol (0.68 g, 5.2 mmol) and triphenylphosphine (1.5 g, 5.8 mmol) in THF (17 mL, 210 mmol). The reaction mixture was warmed to ambient temperature. After 3 h the reaction mixture was quenched with 1 N NaOH and extracted with methylene chloride (3×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified on the Isco (120 g cartridge, hexanes to ethyl acetate).
Workup
- customAfter 3 h the reaction mixture was quenched with 1 N NaOH
- extractionextracted with methylene chloride (3×)
- washThe combined organic layers were washed with brine
- dry with materialdried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residue was purified on the Isco (120 g cartridge, hexanes to ethyl acetate)
Sources & evidence
- ORD record
- ord-1b69d4e09b30414ca0eb17ee395a710e
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08357711B2
Reaction notes
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