Ethanolamine → 3-cyano-N-(2-hydroxyethyl)-4-isopropoxybenzamide

HRID 1807590Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])[C:6]([OH:8])=O)#[N:2].C(Cl)(=O)C(Cl)=O.[CH2:22]([CH2:24][NH2:25])[OH:23]>C(Cl)Cl.CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])[C:6]([NH:25][CH2:24][CH2:22][OH:23])=[O:8])#[N:2]

Participants

Conditions

Temperature: 50 °C

Procedure

To a stirring suspension of 3-cyano-4-isopropoxybenzoic acid (1.0 g, 4.8 mmol) in DCM (20 mL) was added oxalyl chloride (3.7 g, 29.2 mmol) followed by two drops DMF. The reaction mixture was stirred at 50° C. for 2 h. The mixture was concentrated and the residue re-dissolved in DCM (10 mL). Ethanolamine (0.6 g, 9.7 mmol) and TEA (1.45 g, 14.4 mmol) were added and the reaction mixture was stirred overnight at room temperature. The resulting solid was filtered, washed with water, and dried to afford 1.0 g (83%) of 3-cyano-N-(2-hydroxyethyl)-4-isopropoxybenzamide which was used in the next step without purification. LCMS-ESI (ink) calculated for C13H16N2O3: 248.3; found 249.0 [M+H]+, tR=2.41 min. 1H NMR (400 MHz, CDCl3) δ 8.02-7.79 (m, 2H), 6.97-6.87 (m, 1H), 6.71 (s, 1H), 4.65 (dt, J=12.1, 6.1 Hz, 1H), 3.82-3.70 (m, 2H), 3.56 (dd, J=10.2, 5.5 Hz, 2H), 1.96 (d, J=10.0 Hz, 1H), 1.40-1.29 (m, 6H).

Workup

concentrationThe mixture was concentrated
dissolutionthe residue re-dissolved in DCM (10 mL)
stirringthe reaction mixture was stirred overnight at room temperature
filtrationThe resulting solid was filtered
washwashed with water
customdried

Sources & evidence

ORD record: ord-be0f8a5ae9ae4981b7df78a02c14a958
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08357706B2

Reaction notes

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