Sodium Methoxide → (4R)-4-(1-hydroxy-2-methoxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one
Reaction equation
COC1C=CC([C@H](N2C[C@H](C3CO3)CC2=O)C)=CC=1.C[O-].[Na+].[OH:23][C@@H:24]([C@H:28]1[CH2:32][N:31]([C@@H:33]([C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)[CH3:34])[C:30](=[O:43])[CH2:29]1)[CH2:25][O:26][CH3:27]>CO>[OH:23][CH:24]([C@H:28]1[CH2:32][N:31]([C@@H:33]([C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)[CH3:34])[C:30](=[O:43])[CH2:29]1)[CH2:25][O:26][CH3:27]Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 55 °C
Procedure
To a solution of (4R)-1-((R)-1-(4-methoxyphenyl)ethyl)-4-(oxiran-2-yl)pyrrolidin-2-one 1.13 (150 mg, 0.57 mmol) in MeOH (5 mL) was added NaOMe (125 mg, 25% in MeOH), and the solution was heated at 55° C. for 3 hours. The reaction was concentrated and purified by flash chromatography (EtOAc→10% MeOH in EtOAC) to afford the product as a mixture of diastereomers. The isolated mixture was purified by RP-HPLC (C18 Gemini Column) to afford the later eluting diastereomer, which was assigned as (R)-4-((S)-1-hydroxy-2-methoxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.15.
Workup
- concentrationThe reaction was concentrated
- custompurified by flash chromatography (EtOAc→10% MeOH in EtOAC)
- customto afford the product
- additionas a mixture of diastereomers
- customThe isolated mixture was purified by RP-HPLC (C18 Gemini Column)
- customto afford the later eluting diastereomer, which
Sources & evidence
- ORD record
- ord-890e0db69da3460d8d90eb63c5b48485
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09376441B2
Reaction notes
Loading…