(2S,3R)-3-Hydroxypyrrolidine-2-carboxylic acid, N-BOC protected → Isoquinoline
Reaction equation
C(N1CC[C@@H](O)[C@H]1C(O)=O)(OC(C)(C)C)=O.CC(C)([O-])C.[K+].Cl[C:24]1[C:33]2[C:28](=[CH:29][C:30](OC)=[CH:31][CH:32]=2)[CH:27]=[CH:26][N:25]=1>CS(C)=O>[CH:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][N:25]=1Participants
Conditions
- Temperature
- 10 °C
Procedure
To a solution of N-BOC-3-(R)-hydroxy-L-proline (892 mg, 3.89 mmol) in DMSO (40 mL) at the ambient temperature was added potassium tert-butoxide (1.34 g, 12.0 mmol) in one portion. The formed suspension was stirred at this temperature for 30 min before being cooled to 10° C. 1-chloro-6-methoxy-isoquinoline (example 11, Step 2) (785 mg, 4.05 mmol) was added as solid in one portion and the final mixture was stirred at the ambient temperature for 12 h. Quenched with iced 5% citric acid (aq), extracted with EtOAC (100 mL). The aqueous phase was extracted with EtOAC again. The combined organic layers were washed with 5% citric acid (aq) and brine respectively, dried over MgSO4, filtered. The filtrate was evaporated in vacuo to dryness to yield 1.49 g (99%) of the desired product as an off-white foam. This material was used in the next step reaction as crude without further purification.
Workup
- customQuenched with iced 5% citric acid (aq)
- extractionextracted with EtOAC (100 mL)
- extractionThe aqueous phase was extracted with EtOAC again
- washThe combined organic layers were washed with 5% citric acid (aq) and brine respectively
- dry with materialdried over MgSO4
- filtrationfiltered
- customThe filtrate was evaporated in vacuo to dryness
Sources & evidence
- ORD record
- ord-2d5653aac1124276bdca55a1c0e1d034
- Source dataset
- uspto-grants-2007_02
- Patent number
- US07173004B2
Reaction notes
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