Isopropanol → 3-(2-methoxy-5-pyrimidinyl)Pentanedioic acid

HRID 1182347Notes

Reaction equation

[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([CH:9]=O)=[CH:5][N:4]=1.C([O:13][C:14](=[O:19])[CH2:15]C(C)=O)C.N1CCCCC1.[OH-:26].[Na+].C[CH:29]([OH:31])[CH3:30]>>[C:29]([CH2:30][CH:9]([C:6]1[CH:7]=[N:8][C:3]([O:2][CH3:1])=[N:4][CH:5]=1)[CH2:15][C:14]([OH:13])=[O:19])([OH:31])=[O:26]

Participants

Reactant 5

HCID 3776Isopropanol

HCID 8082Piperidine

HCID 8868Ethyl Acetoacetate

HCID 14798Sodium Hydroxide

HCID 31518662-Methoxypyrimidine-5-carboxaldehyde

Product 1

HCID 112764933-(2-methoxy-5-pyrimidinyl)Pentanedioic acidYield 85%

Procedure

2-Methoxypyrimidine-5-carbaldehyde (see J. Heterocycl. Chem. (1991) 28, 1281) (9.00 kg) was reacted with ethylacetoacetate (17.8 kg) in the presence of piperidine (555 g) in propan-2-ol (90 L) at 50° C. for several hours, followed by a hydrolysis with aqueous sodium hydroxide (24.2 kg of 46% NaOH in 30 L of water) at 0° C. Phase separation of the resulting mixture, acidification of the aqueous layer with concentrated hydrochloric acid (23.2 kg) to pH 2-3 and crystallization afforded the title compound (12.7 kg; 85% yield).

Workup

customPhase separation of the resulting mixture, acidification of the aqueous layer with concentrated hydrochloric acid (23.2 kg)
customto pH 2-3 and crystallization

Sources & evidence

ORD record: ord-7bbb65c7500240ba94317c413fd22477
Source dataset: uspto-grants-2007_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07288655B2

Reaction notes

Loading…