Ethyl Acetoacetate → Ethyl 3-(3-methylphenyl)-3-oxopropanoate

HRID 1156601Notes

Reaction equation

HRID 1156601 reaction equation
[C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[OH-].[Na+].[C:12]1([CH3:21])[CH:17]=C[CH:15]=[C:14](C(Cl)=O)[CH:13]=1.[Na].C1(C)C=CC=C(C(CC(=O)CC(OCC)=O)=O)C=1.[Cl-].[NH4+]>O.C1C=CC=CC=1>[C:12]1([CH3:21])[CH:13]=[CH:14][CH:15]=[C:5]([C:3]([CH2:2][C:1]([O:7][CH2:8][CH3:9])=[O:6])=[O:4])[CH:17]=1

Participants

9

Reactant 6

HCID 8868Ethyl AcetoacetateHCID 14798Sodium Hydroxide2×HCID 25517Ammonium ChlorideHCID 743753-Methylbenzoyl chlorideHCID 5360545SodiumHCID 53727442HCID 53727442, compound

Product 1

HCID 2760277Ethyl 3-(3-methylphenyl)-3-oxopropanoateYield 17.5%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 962WaterSolvent

Procedure

To a cold (5° C.) mixture of 137.5 g (1.05 mole) of ethyl acetoacetate, 175 ml. of benzene, 325 ml. of water, and 45.8 ml. of 33% sodium hydroxide was added simultaneously 221.05 g (1.430 mole) of m-toluoyl chloride and 190 ml. of 33% sodium hydroxide as described in Example 4. The aqueous solution of sodium salt of ethyl m-toluoylacetoacetate was stirred with 56.3 g of ammonium chloride overnight and worked up as described in Example 4 to give 38.0 g (17%) of crude ethyl m-toluoylacetate after a Kugelrohr distillation (95°-98° C. at 0.05 mm Hg). A mixture of 20.6 g (0.1 mole) of crude ethyl m-toluoylacetate, 13.6 g (0.105 mole) of sulfuryl chloride, and 30 ml. of chloroform was held at reflux for 6 hours and worked up as described in Example 4 to give 25.0 g of ethyl 2-chloro-m-toluoylacetate, which was used directly as described below. A mixture of 22.5 g (0.1 mole) of ethyl 2-chloro-m-toluoylacetate, 7.6 g (0.1 mole) of thiourea and 100 ml. of ethanal was held at reflux for 2 hours and worked up as described in Example 4 to give 23.0 g of solid, which was recrystallized from ethanol to give 11.6 g (44%) of ethyl 2-amino-4-(m-tolyl)-5-thiazolecarboxylate, m.p. 185°-187° C. An additional 4.5 g (17%) of less pure ethyl 2-amino-4-(m-tolyl)-5-thiazolecarboxylate, m.p. 183°-184° C. was obtained by concentration of the mother liquor. To a cold (-5° C.) mixture of 10.5 g (0.04 mole) of ethyl 2-amino-4-(m-tolyl)-5-thiazolecarb and 80 ml. of 85% phosphoric acid was added 40 ml. of 70% nitric acid. To the vigorously stirred above mixture was added 3.0 g (0.0434 mole) of sodium nitrite in 20 minutes. The reaction mixture was stirred for 10 minutes and poured into a mixture of 4.0 g (0.04 mole) of cuprous chloride, 20 ml. of concentrated hydrochloric acid and 20 ml. of water. After the gas evolution had subsided the reaction mixture was extracted with ether, dried (MgSO4) and concentrated under reduced pressure to give 10 g of oil which was Kugelrohr distilled (135°-140° C. at 0.05 mm) to give 6.5 g of oil, which was crystallized from ethanol to give 3.9 g (34%) of the desired product as a white solid, m.p. 41°-42° C.

Sources & evidence

ORD record
ord-bab297b9acef47568726b3eee0322d7a
Source dataset
uspto-grants-1982_06
Patent number
US04336389

Reaction notes

Loading…