Malonic Acid → HCID 89955318, compound

A suspension of 3-chloro-5-(2-hydroxypropan-2-yl)benzaldehyde (2.35 g, 11.83 mmol), malonic acid (1.50 g, 14.41 mmol) and ammonium acetate (1.85 g, 24.00 mmol) in isopropanol (30.0 mL) was heated at reflux under nitrogen atmosphere for 4 h to afford a colorless suspension in a yellow-orange solution. The hot reaction mixture was filtered and the solid was washed with hot isopropanol (2×25 mL) and discarded. The filtrate was evaporated in vacuo to afford a mixture of the desired acid (40%) and the byproduct: 3-(3-chloro-5-(2-hydroxypropan-2-yl)phenyl)acrylic acid (60%) as a cream yellow foamy solid. The solid was recrystallized several times (×5) from ethyl acetate to afford the pure desired product, free from the byproduct impurity, as a colorless solid (632.8 mg). LC-MS analysis of the solid shows the desired product's mass: m/z 258 (35ClM+H), m/z 260 (37ClM+H), m/z 240 (35ClM+H−H2O) and m/z 242 (37ClM+H−H2O); Calcd for C12H16ClNO3: 257.71. 1H NMR (400 MHz, DMSO-d6): δ 1.42 (s, 6H, (CH3)2C—), 2.30 (dd, J=8.0 and 6.0 Hz, 2H, —CH2—COOH), 4.21 (appt, J=7.0 Hz, 1H, —NH—CH—CH2—COOH), 6.33 (s, 1H, (CH3)2—C—OH), 7.31 (appt, J=1.60 Hz, 1H), 7.38 (appt, J=1.70 Hz, 1H), 7.42 ((d, J=9.0 Hz, 1H). 1H NMR spectrum of the sample was consistent with the suggested structure of the product.

1. temperaturewas heated
2. temperatureat reflux under nitrogen atmosphere for 4 h
3. customto afford a colorless suspension in a yellow-orange solution
4. filtrationThe hot reaction mixture was filtered
5. washthe solid was washed with hot isopropanol (2×25 mL)
6. customThe filtrate was evaporated in vacuo
7. customto afford
8. customThe solid was recrystallized several times (×5) from ethyl acetate

ORD record

ord-ada2ebc29b5b438288a5dc69ec979e10

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09085606B2