Toluene → Methyl (2s)-2-ethyl-2,3-dihydro-1-benzofuran-2-carboxylate
Reaction equation
F[C:2]1[CH:15]=[CH:14][CH:13]=[CH:12][C:3]=1[CH2:4][C@@:5]([OH:11])([CH2:9][CH3:10])[C:6]([OH:8])=[O:7].[CH3:16]N(C=O)C.C1(C)C=CC=CC=1.[H-].[Na+]>O>[CH2:9]([C@@:5]1([C:6]([O:8][CH3:16])=[O:7])[CH2:4][C:3]2[CH:12]=[CH:13][CH:14]=[CH:15][C:2]=2[O:11]1)[CH3:10]Participants
Conditions
- Temperature
- 110 °C
Procedure
To a solution of the acid from step 1 (4.0 g, ca. 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 methyl (2S)-2-ethyl-2,3-dihydro-benzofuran-2-carboxylate.
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
- additionMeOH (80 mL) and treated 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-f792c5cd496448999b4a07e13277c14c
- Source dataset
- uspto-grants-2009_04
- Patent number
- US07524882B2
Reaction notes
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