Reaction equation
[C:1]([O:5][C:6](=[O:17])[C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[C:9]([N+:14]([O-:16])=[O:15])[CH:8]=1)([CH3:4])([CH3:3])[CH3:2].C=O.C[C:21]([O-:24])(C)C.[K+]>CS(C)=O>[C:1]([O:5][C:6](=[O:17])[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:21][OH:24])=[C:9]([N+:14]([O-:16])=[O:15])[CH:8]=1)([CH3:4])([CH3:2])[CH3:3]Participants
Procedure
A solution of 4-methyl-3-nitro-benzoic acid tert-butyl ester (8.66 g, 36.5 mmol) in anhydrous DMSO (135 mL) was treated with paraformaldehyde (1.32 g, 44.0 mmol, 1.2 eq.) followed by t-BuOK (0.32 g, 2.7 mmol, 0.074 eq.). The mixture was stirred at room temperature for 2.5 h and quenched with aqueous NH4Cl (250 mL). The mixture was extracted with ethyl acetate (3×50 mL) and the combined organic layers were washed with brine and water, and then dried (Na2SO4) and concentrated. Silica gel chromatography using ethyl acetate (0→30%) in dichloromethane provided 4-(2-hydroxy-ethyl)-3-nitro-benzoic acid tert-butyl ester (4.8 g, white solid): 1H NMR (400 MHz, CDCl3) δ 8.47 (d, 1H), 8.13 (dd, 1H), 7.49 (d, 1H), 3.96 (q, 2H), 3.20 (t, 2H), 1.60 (s, 9H), and 4-(2-hydroxy-1-hydroxymethyl-ethyl)-3-nitro-benzoic acid tert-butyl ester (3.7 g, white solid): 1H NMR (400 MHz, CDCl3) δ 8.35 (d, 1H), 8.15 (dd, 1H), 7.65 (d, 1H), 4.05 (t, 4H), 3.61 (Q, 1H), 2.05 (t, 2H), 1.59 (s, 9H).
Workup
- customquenched with aqueous NH4Cl (250 mL)
- extractionThe mixture was extracted with ethyl acetate (3×50 mL)
- washthe combined organic layers were washed with brine and water
- dry with materialdried (Na2SO4)
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-9a863a860bb842608fcd2fced3cda9bf
- Source dataset
- uspto-grants-2012_04
- Patent number
- US08148391B2
Linked notes
Loading…