Sodium Hydroxide → Ethyl 2,2-dimethylchroman-6-carboxylate

HRID 1417638

반응식

HRID 1417638 반응식
[CH3:1][C:2]1([CH3:12])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[O:3]1.C(C1C=C2[C:23](=CC=1)[O:22][C:21](C)(C)[CH2:20]C2)(=O)C.[O-:28]Cl.[Na+].[OH-].[Na+]>>[CH3:1][C:2]1([CH3:12])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:23]([O:22][CH2:21][CH3:20])=[O:28])[CH:8]=2)[O:3]1

참가 물질

5

반응물 4

HCID 14798Sodium HydroxideHCID 1369362,2-DimethylchromanHCID 1820772,2-Dimethyl-6-acetylchroman2회HCID 23665760Sodium Hypochlorite

생성물 1

HCID 246672Ethyl 2,2-dimethylchroman-6-carboxylate

실험 절차

Reaction Scheme 6B discloses a synthetic route to specific preferred benzopyran (chromene) compounds of the invention where with reference to Formula 1 the Z group is also CONH (amide derivatives). In accordance with this scheme, dihydrocoumarine (Compound 213) is subjected to a Grignard reaction with methyl magnesium chloride followed by heating a tertiary alcohol intermediate with acid, to provide 2,2-dimethylchroman (Compound 214). Compound 214 is converted into 6-acetyl-2,2-dimethylchroman (Compound 215) in a Friedel--Crafts reaction, and the latter is oxidized with NaOCl in the presence of sodium hydroxide and thereafter esterified to give ethyl 2,2-dimethylchroman-6-carboxylate (Compound 216). Compound 216 is treated with bromine in glacial acetic acid to give ethyl 8-bromo-2,2-dimethylchroman-6-carboxylate (Compound 217). Compound 217 is oxidized with chromium trioxide to form a ketone function in the 4-position of the chroman ring and yield ethyl 8-bromo-2,2-dimethyl-4-chromanone-6-carboxylate (Compound 218). Reaction of Compound 218 with the Grignard reagent made from 4-bromotoluene, and subsequent heating with p-TSOH to complete dehydration of the intermediate tertiary alcohol, provides ethyl 8-bromo-2,2-dimethyl-4-tolyl-4(2H)-chroman-6-carboxylate (Compound 219). Saponification of Compound 219 with base gives the corresponding free carboxylic acid, 8-bromo-2,2-dimethyl-4-tolyl-4(2H)-chroman-6-carboxylic acid (Compound 220). Compound 220 is condensed with ethyl 2-fluoro-4-aminobenzoate and ethyl 2,6-difluoro-4-aminobenzoate, in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and of 4-dimethylaminopyridine (DMAP) to provide ethyl 2-fluoro-4-[[8-bromo-2,2-dimethyl-4-tolyl-6-chromanyl)carbonyl]amino]-benzoate (Compound 221) and ethyl 2,6-difluoro-4-[[8-bromo-2,2-dimethyl-4-tolyl-6-chromanyl)carbonyl]amino]-benzoate (Compound 222), respectively. Saponification of Compounds 221 and 222 yields the corresponding free carboxylic acids, 2-fluoro-4-[[8-bromo-2,2-dimethyl-4-tolyl-6-chromanyl)carbonyl]amino]-benzoic acid (Compound 204) and 2,6-difluoro-4-[[8-bromo-2,2-dimethyl-4-tolyl-6-chromanyl)carbonyl]amino]-benzoic acid (Compound 205), respectively. ##STR14##

후처리

  1. customCrafts reaction

출처 및 근거

ORD 기록
ord-23da1337b6724db1abef4ecb2f1c1c94
출처 데이터셋
uspto-grants-1999_03
특허 번호
US05877207

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