tert-Butyl acetate → 3-[5-(2,2-Dimethyl-propionylamino)-pyrazin-2-yl]-3-oxo-propionic acid-tert-butyl ester

HRID 11998

반응식

HRID 11998 반응식
[C:1]([O:4][C:5]([CH3:8])([CH3:7])[CH3:6])(=[O:3])[CH3:2].C[O:10][C:11]([C:13]1[CH:18]=[N:17][C:16]([NH:19][C:20](=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:15][N:14]=1)=O.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[C:5]([O:4][C:1](=[O:3])[CH2:2][C:11]([C:13]1[CH:18]=[N:17][C:16]([NH:19][C:20](=[O:25])[C:21]([CH3:23])([CH3:22])[CH3:24])=[CH:15][N:14]=1)=[O:10])([CH3:8])([CH3:7])[CH3:6]

참가 물질

5

반응물 3

HCID 10908tert-Butyl acetateHCID 2733832Lithium HexamethyldisilazideHCID 442485015-(2,2-Dimethyl-propionylamino)-pyrazine-2-carboxylic acid methyl ester

생성물 1

HCID 685835183-[5-(2,2-Dimethyl-propionylamino)-pyrazin-2-yl]-3-oxo-propionic acid-tert-butyl ester

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-20 °C

실험 절차

A 3-necked 1-L round bottomed flask equipped with a magnetic stirrer, addition funnel, thermocouple probe and nitrogen inlet/outlet was charged with 25.00 mL (185.5 mmol) of tert-butyl acetate, 20.00 g (84.30 mmol) of the compound prepared in step 2 and 20 mL of THF. After cooling to −20° C., a solution of 261.4 mL (261.4 mmol) of 10M lithium bis(trimethylsilyl)amide (LHMDS) in THF was added dropwise, while maintaining the temperature of the reaction mixture between −20° C. and 0° C. The resulting red solution was stirred at −20° C. for 40 min. HPLC analysis indicated complete reaction. The mixture was allowed to warm to 0° C., then quenched by the addition of pre-cooled 200 mL (260.3 mmol) of 25 wt % citric acid solution. The organic layer was separated, washed with 2×200 mL of saturated sodium chloride solution and concentrated at 30° C./60 mmHg to a volume of ca. 50 mL. The concentrated solution was diluted with 200 mL of butanone and again concentrated at 30° C./60 mmHg to ca. 50 mL. The concentrate was again diluted with 200 mL of butanone and concentrated at 30° C./60 mmHg to a volume of ca. 100 mL. NMR analysis indicated the absence of THF. The resulting butanone solution of the title compound was used directly in the next step.

후처리

  1. customA 3-necked 1-L round bottomed flask equipped with a magnetic stirrer, addition funnel
  2. temperaturewhile maintaining the temperature of the reaction mixture between −20° C. and 0° C
  3. customreaction
  4. temperatureto warm to 0° C.
  5. customquenched by the addition of pre-cooled 200 mL (260.3 mmol) of 25 wt % citric acid solution
  6. customThe organic layer was separated
  7. washwashed with 2×200 mL of saturated sodium chloride solution
  8. concentrationconcentrated at 30° C./60 mmHg to a volume of ca. 50 mL
  9. additionThe concentrated solution was diluted with 200 mL of butanone
  10. concentrationagain concentrated at 30° C./60 mmHg to ca. 50 mL
  11. additionThe concentrate was again diluted with 200 mL of butanone
  12. concentrationconcentrated at 30° C./60 mmHg to a volume of ca. 100 mL

출처 및 근거

ORD 기록
ord-c52e6a4d4f9a43eb8ee7ebb98fc9064c
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727750B2

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