Ethyl isoquinoline-4-carboxylate → HCID 69710287, compound

Isoquinoline4-carboxylic acid ethyl ester (85.7 g, 0.426 mol) is dissolved in HOAc (1000 ml) and hydrogenated at 150 bar and 60° for 2 h in the presence of 5% Rh/C (86 g). The mixture is filtered and the filtrate evaporated. The residue is dissolved in MTBE (500 ml) and washed with 2N KHCO3 (400 ml) and brine (100 ml). The combined water phases are exhaustively extracted with DCM (3×150 ml), the extracts dried over Na2SO4 and evaporated to yield the crude acetate salt of the desired product. Recrystallization from DCM/Et2O yields the pure acetate salt. This salt is dissolved in water (200 ml) and cooled to 0°. Cold 2N NaOH (150 ml) is slowly added and the mixture extracted with DCM (1×250 ml, 2×150 ml, 1×100 ml). The extracts are dried (Na2SO4) and evaporated. The residue is crystallised from 300 ml hexanes at −20° to yield the pure product as a white crystal powder, m.p. 44°-52°. TLC (silicagel, EtOAc/MeOH/NH4OH 85:15:1): rf 0.25. Two further portions can be crystallised from the mother liquor with somewhat lower melting points (42°-52° and 38°-51°).

1. filtrationThe mixture is filtered
2. customthe filtrate evaporated
3. dissolutionThe residue is dissolved in MTBE (500 ml)
4. washwashed with 2N KHCO3 (400 ml) and brine (100 ml)
5. extractionThe combined water phases are exhaustively extracted with DCM (3×150 ml)
6. dry with materialthe extracts dried over Na2SO4
7. customevaporated

ORD record

ord-1a7773472b324c808757e53555e2ad73

Source dataset

uspto-grants-2003_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06635647B2