Sodium hydride → Methyl (2s)-2-ethyl-2,3-dihydro-1-benzofuran-2-carboxylate
Reaction equation
[CH2:1]([C@:3]([OH:15])([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1F)[C:4]([OH:6])=[O:5])[CH3:2].[CH3:16]N(C=O)C.C1(C)C=CC=CC=1.[H-].[Na+]>O>[CH2:1]([C@@:3]1([C:4]([O:6][CH3:16])=[O:5])[CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[O:15]1)[CH3:2]Participants
Conditions
- Temperature
- 110 °C
Procedure
To a solution of the product from Step 3 (4.0 g, 20 mmol) in 1:4 DMF/toluene (100 mL) was added 60% NaH in mineral oil (1.76 g, 44 mmol) in 3 portions. The reaction mixture was stirred at 110° C. under N2 for 4 hrs. The reaction was cooled to room temperature and poured into cold water (100 mL). The aqueous layer was washed with hexane (50 mL), acidified with 2 N aqueous HCl and extracted with ethyl acetate (3×50 mL). The extracts were washed with brine (50 mL), dried and concentrated. The residue was dissolved in 7:1 benzene/MeOH (80 mL) and treated with TMSCHN2 (1M in hexane) until gas evolution ceased. The reaction was concentrated and the residue was chromatographed on silica gel eluting with 85:15 hexane:ethylacetate to give the title compound
Workup
- temperatureThe reaction was cooled to room temperature
- washThe aqueous layer was washed with hexane (50 mL)
- extractionextracted with ethyl acetate (3×50 mL)
- washThe extracts were washed with brine (50 mL)
- customdried
- concentrationconcentrated
- dissolutionThe residue was dissolved in 7:1 benzene/MeOH (80 mL)
- additiontreated with TMSCHN2 (1M in hexane) until gas evolution
- concentrationThe reaction was concentrated
- customthe residue was chromatographed on silica gel eluting with 85:15 hexane
Sources & evidence
- ORD record
- ord-137c58feff304dd9af7138ea28d4c564
- Source dataset
- uspto-grants-2009_12
- Patent number
- US07629372B2
Reaction notes
Loading…