Hydrochloric Acid → 4-Benzyloxy-3-cyclopentyl-benzaldehyde
Reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][C:10]=1[CH:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.CN([CH:29]=[O:30])C.Cl>O1CCCC1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:29]=[O:30])=[CH:11][C:10]=1[CH:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1Participants
Conditions
- Temperature
- -65 °C
Procedure
A stirred solution of 1-benzyloxy-4-bromo-2-cyclopentyl-benzene (1500 mg, 4.53 mmol) in tetrahydrofuran (13.4 mL) was cooled to −65° C. n-BuLi (3.11 mL of 1.6 M, 4.98 mmol) was added dropwise over several minutes. After 30 min, DMF (497 mg, 526.0 μL, 6.79 mmol) was added dropwise over a period of 10 min. Stirring at −65° C. was maintained for 20 min, and then the reaction was quenched by the addition of HCl (9.06 mL of 1 M, 9.06 mmol). The aqueous and organic layers were separated. The organic layer was washed with saturated NaHCO3 (10 mL) and water (10 mL), dried over Na2SO4, filtered and concentrated. Purification by silica gel chromatography (0-10% ethyl acetate/hexanes) provided 4-benzyloxy-3-cyclopentyl-benzaldehyde (800 mg, 63% yield) white solid. 1H NMR (400.0 MHz, DMSO-d6) δ 9.86 (s, 1H), 7.76 (dd, J=2.1, 6.6 Hz, 2H), 7.49-7.29 (m, 5H), 7.26-7.20 (m, 1H), 5.26 (s, 2H), 3.37-3.26 (m, 1H), 2.00-1.90 (m, 2H), 1.73-1.50 (m, 6H).
Workup
- additionwas added dropwise over several minutes
- temperaturewas maintained for 20 min
- customThe aqueous and organic layers were separated
- washThe organic layer was washed with saturated NaHCO3 (10 mL) and water (10 mL)
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
- customPurification by silica gel chromatography (0-10% ethyl acetate/hexanes)
Sources & evidence
- ORD record
- ord-796aa8b85b5b4ca2b0b950fd99e97097
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08633189B2
Reaction notes
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