Methanol → HCID 58884958, compound

HRID 726951Notes

Reaction equation

HRID 726951 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([NH2:11])[S:9][CH:10]=1)=[O:5])[CH3:2].C(N(CC)CC)C.[CH3:19][C:20]([C:23]1[CH:24]=[C:25]([CH:29]=[C:30]([C:33]([CH3:36])([CH3:35])[CH3:34])[C:31]=1[OH:32])[C:26](Cl)=[O:27])([CH3:22])[CH3:21].CO>O1CCCC1.C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([NH:11][C:26]([C:25]2[CH:24]=[C:23]([C:20]([CH3:19])([CH3:21])[CH3:22])[C:31]([OH:32])=[C:30]([C:33]([CH3:36])([CH3:35])[CH3:34])[CH:29]=2)=[O:27])[S:9][CH:10]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 73216Ethyl 2-aminothiazole-4-carboxylateHCID 37871873,5-Di-tert-butyl-4-hydroxybenzoyl chloride

Product 1

HCID 58884958HCID 58884958, compoundYield 36.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

2-Amino-4-thiazolecarboxylic acid ethyl ester (16.2 g, 100 mmol) and triethylamine (TEA, 10.5 g, 104 mmol) were combined in anhydrous tetrahydrofuran (THF, 200 mL) in a nitrogen atmosphere. To this was added slowly with stirring a solution of 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzoylchloride (28 g, 104 mmol) in THF (100 mL). The reaction mixture was heated under reflux and monitored for disappearance of starting material by TLC (silica gel, 2% methanol in methylene chloride). After two days, the reaction mixture was cooled to room temperature and filtered to give 14.67 g of 2-[[[3,5-Bis(1,1-dimethylethyl)-4-hydroxyphenyl]-carbonyl]-amino]-4-thiazolecarboxylic acid ethyl ester as a white solid, m.p. 233°-235° C. The filtrate was poured into ice water and extracted five times with diethyl ether. The ether phase was dried and evaporated and the residue was purified by flash chromatography on silica gel eluting with 20:80 hexane:methylene chloride to give 29.41 g of additional ethyl ester.

Workup

  1. additionTo this was added slowly
  2. temperatureThe reaction mixture was heated
  3. temperatureunder reflux
  4. filtrationfiltered

Sources & evidence

ORD record
ord-b7da8d8d383f4f7ab48705a264d12d3c
Source dataset
uspto-grants-1998_01
Patent number
US05712270

Reaction notes

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