Isobutyraldehyde → HCID 68156815, compound
Reaction equation
I[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.[CH:13](=O)[CH:14]([CH3:16])[CH3:15].[O:18]1CCC[CH2:19]1>>[CH2:9]([O:8][C:6](=[O:7])[C:5]1[CH:11]=[CH:12][C:2]([CH:19]([OH:18])[CH2:13][CH:14]([CH3:16])[CH3:15])=[CH:3][CH:4]=1)[CH3:10]Participants
Procedure
To a solution of ethyl 4-iodobenzoate (140 g, 507 mmol) in tetrahydrofuran at −40° C. was added Isopropylmagnesium chloride lithium chloride complex solution (1.0 M in tetrahydrofuran, 429 mL, 558 mmol) dropwise at a rate to maintain the internal temperature below −30° C. The mixture was stirred for 30 minutes at which point isobutyraldehyde (61 g, 710 mmol) was added dropwise while maintaining the temperature below −35° C. The mixture was stirred at this temperature for 15 minutes and then slowly warmed to room temperature. The reaction was quenched with 1N HCl (3 L) and the mixture extracted with ethyl acetate (2 L×2). The combined organics were washed with brine (1 L) and water (1 L), and then dried over anhydrous Na2SO4. This was concentrated in vacuo to give (+/−)-4-(1-hydroxy-3-methyl-butyl)-benzoic acid ethyl ester (120 g, 100%) as an oil. 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J=8.4 Hz, 2 H), 7.47 (s, J=7.2 Hz, 2 H), 4.76-4.73 (m, 1 H), 4.33-4.28 (m, 2 H), 1.71-1.60 (m, 2 H), 1.46-1.41 (m, 1 H), 1.39-1.31 (m, 3 H), 0.92-0.87 (m, 6 H).
Workup
- temperatureto maintain the internal temperature below −30° C
- additionwas added dropwise
- temperaturewhile maintaining the temperature below −35° C
- customThe reaction was quenched with 1N HCl (3 L)
- extractionthe mixture extracted with ethyl acetate (2 L×2)
- washThe combined organics were washed with brine (1 L) and water (1 L)
- dry with materialdried over anhydrous Na2SO4
- concentrationThis was concentrated in vacuo
Sources & evidence
- ORD record
- ord-fc5b8b566696416b90a2fdf29593e74d
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09139538B2
Reaction notes
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