Methanol → 1-(4-Hydroxy-4-methoxychroman-6-yl)cyclopropanecarboxylic acid
Reaction equation
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]3([C:15]([O:17]C)=[O:16])[CH2:14][CH2:13]3)[CH:10]=2)[O:5][CH2:4][CH2:3]1.O[Li].[OH2:21].[CH3:22]O>O>[OH:1][C:2]1([O:21][CH3:22])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]3([C:15]([OH:17])=[O:16])[CH2:13][CH2:14]3)[CH:10]=2)[O:5][CH2:4][CH2:3]1Participants
Procedure
To a solution of methyl 1-(4-oxochroman-6-yl)cyclopropanecarboxylate (1.0 g, 4.1 mmol) in MeOH (20 mL) and water (20 mL) was added LiOH.H2O (0.70 g, 16 mmol) in portions at room temperature. The mixture was stirred overnight at room temperature before the MeOH was removed by evaporation under vacuum. Water and Et2O were added to the residue and the aqueous layer was separated, acidified with HCl and extracted with EtOAc (50 mL×3). The combined organic extracts dried over anhydrous Na2SO4 and evaporated under vacuum to give 1-(4-hydroxy-4-methoxychroman-6-yl)cyclopropanecarboxylic acid (480 mg, 44%). 1H NMR (400 MHz, CDCl3) δ 12.16 (s, 1H), 7.73 (d, J=2.0 Hz, 1H), 7.47 (dd, J=2.0, 8.4 Hz, 1H), 6.93 (d, J=8.8 Hz, 1H), 3.83-3.80 (m, 2H), 3.39 (s, 3H), 3.28-3.25 (m, 2H), 1.71-1.68 (m, 2H), 1.25-1.22 (m, 2H). MS (ESI) m/z (M+H+) 263.1.
Workup
- customwas removed by evaporation under vacuum
- additionWater and Et2O were added to the residue
- customthe aqueous layer was separated
- extractionextracted with EtOAc (50 mL×3)
- dry with materialThe combined organic extracts dried over anhydrous Na2SO4
- customevaporated under vacuum
Sources & evidence
- ORD record
- ord-be707a2eed9248f5900d33d6094f4011
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08598181B2
Reaction notes
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