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

HRID 55732

반응식

HRID 55732 반응식
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

참가 물질

8

반응물 5

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

생성물 1

HCID 3146282-Amino-thiazole-5-carboxylic acid ethyl ester수율 137%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매3회

반응 조건

온도
0 °C

실험 절차

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, mp. 155°-158° C.

후처리

  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. temperatureto warm to 15° C.
  5. temperatureThe solution was warmed to 65° C.
  6. temperaturerefluxed for 1 hour
  7. temperaturecooled to 30° C
  8. customproduced two layers (aqueous pH=7)
  9. customThe THF was removed under vacuum at ≤45° C.
  10. customto precipitate as a yellow solid
  11. temperatureThe slurry was cooled to 15° C.
  12. customthe product was collected on a fritted Buchner funnel
  13. washwashed with 3×200 mL water
  14. customdried 24 hours in a vacuum oven at 55° C.

출처 및 근거

ORD 기록
ord-ff085995381c441daf894092d06547be
출처 데이터셋
uspto-grants-1997_04
특허 번호
US05625072

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