Ethyl chloroacetate → 2-Amino-thiazole-5-carboxylic acid ethyl ester

HRID 52743

反応式

HRID 52743 の反応式
CC(C)([O-])C.[K+].Cl[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10].C(OCC)=O.[NH2:19][C:20]([NH2:22])=[S:21].[C:23]([O-])([O-])=O.[K+].[K+]>C1COCC1.O>[NH2:19][C:20]1[S:21][C:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:23][N:22]=1

参加物

8

反応物 5

HCID 7751Ethyl chloroacetateHCID 8025Ethyl formateHCID 11430Potassium CarbonateHCID 2723790ThioureaHCID 23665647Potassium tert-butoxide

生成物 1

HCID 3146282-Amino-thiazole-5-carboxylic acid ethyl ester収率 137%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
15 °C

実験手順

To a -10° C. solution of potassium tert-butoxide (150 g, 1.3 mol) in THF (1.35 L) was added a solution of ethyl chloroacetate (139 mL, 1.3 mol) and ethyl formate (103 mL, 1.27 mol) in THF (150 mL) dropwise over 75 minutes, with good mechanical stirring. A THF rinse (25 mL) was added over 5 minutes. The thick solution was stirred another 3 hours at ca. -5° to 0° C.,then the reaction was quenched by addition of a solution of NaCl (240 g) and conc. HCl (90 mL) in water (960 mL). The mixture was allowed to warm to 15° C. and the lower aqueous layer was discarded. Thiourea (97 g, 1.27 mol) was dissolved in the crude THF solution of chloroaldehyde. The solution was warmed to 65° C. and refluxed for 1 hour, then cooled to 30° C. Addition of a solution of K2CO3 (88 g, 0.64 mol) in 1500 mL water produced two layers (aqueous pH=7). The THF was removed under vacuum at ≤45° C., causing the product to precipitate as a yellow solid. The slurry was cooled to 15° C., and the product was collected on a fritted Buchner funnel and washed with 3×200 mL water, then dried 24 hours in a vacuum oven at 55° C. to provide 151 g of title compound as a yellow solid, m.p. 155°-158° C. 1H NMR (DMSO-d6) δ7.8 (br s, 2H, NH2), 7.62 (s, 1H), 4.13 (q, 2H), 1.18 (t, 3H). 13C NMR (DMSO-d6) δ173.4, 161.3, 147.9, 114.5, 60.1, 14.3.

後処理

  1. washA THF rinse (25 mL)
  2. additionwas added over 5 minutes
  3. customthe reaction was quenched by addition of a solution of NaCl (240 g) and conc. HCl (90 mL) in water (960 mL)
  4. temperatureThe solution was warmed to 65° C.
  5. temperaturerefluxed for 1 hour
  6. temperaturecooled to 30° C
  7. customproduced two layers (aqueous pH=7)
  8. customThe THF was removed under vacuum at ≤45° C.
  9. customto precipitate as a yellow solid
  10. temperatureThe slurry was cooled to 15° C.
  11. customthe product was collected on a fritted Buchner funnel
  12. washwashed with 3×200 mL water
  13. customdried 24 hours in a vacuum oven at 55° C.

出典と根拠

ORDレコード
ord-6731a7f00bc544bebc2b16767477c724
出典データセット
uspto-grants-1997_04
特許番号
US05616720

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