Water → HCID 10138368, 화합물

HRID 1062288노트

반응식

HRID 1062288 반응식
C([Si](C)(C)[O:6][CH2:7][CH2:8][CH2:9][O:10][NH:11][C:12](=[O:29])[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=1[NH:20][C:21]1[CH:26]=[CH:25][C:24]([I:27])=[CH:23][C:22]=1[CH3:28])(C)(C)C.OS(O)(=O)=O.O>CO>[F:19][C:16]1[CH:17]=[CH:18][C:13]([C:12]([NH:11][O:10][CH2:9][CH2:8][CH2:7][OH:6])=[O:29])=[C:14]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([I:27])=[CH:23][C:22]=2[CH3:28])[CH:15]=1

참가 물질

5

반응물 3

HCID 962WaterHCID 1118Sulfuric Acid2회HCID 22286093HCID 22286093, 화합물

생성물 1

HCID 10138368HCID 10138368, 화합물수율 74.3%

시약·촉매·용매 1

HCID 887Methanol용매3회

실험 절차

To a solution of N-[3-(tert-Butyl-dimethyl-silanyloxy)-propoxy]-4-fluoro-2-(4-iodo-2-methyl-phenylamino)-benzamide (4.0 g, 7.27 mmol) in methanol (5 mL) at ambient temperature was added 5 M H2SO4 in methanol (0.073 mL, 0.364 mmol). After 1 h of stirring, to the reaction was added additional 5 M H2SO4 in methanol (0.035 mL, 0.182 mmol). After 2 h of stirring, the reaction was adjusted to pH 7 using saturated NaHCCO3 (aq) (c. a. 1.5 mL), followed by addition of water (35 mL). The aqueous layer was extracted with ethyl acetate (1×20 mL, 2×10 mL). The extracts were combined, washed with brine, and dried over magnesium sulfate. The resultant mixture was filtered, and the filtrate solvent was removed in vacuo to obtain an oil that was dried on a vacuum pump over the weekend. The oil was purified by flash chromatography, eluted with a gradient of 100% hexanes to 100% ethyl acetate in 50 min. The solvent was removed in vacuo of combined fractions to obtain a solid which was dried on a vacuum pump for c. a. 6 h. Recrystalized solid in a mixture of hexanes and ethyl acetate to afford 4-fluoro-N-(3-hydroxy-propoxy)-2-(4-iodo-2-methyl-phenylamino)-benzamide as a solid (2.4 g, 74% yield): m.p. 120.8-122.4 C.; 1H-NMR (400 MHz, (CD3)2CO) δ 10.91 (br s, 1H), 9.59 (br. S, 1H), 9.68 (m, 2H), 7.57 (d, 1H, J=8.54 Hz), 7.18 (d, 1H, J=8.34 Hz), 6.72 (m, 1H); 6.53 (m, 1H); 4.12 (t, 2H, J=6.11 Hz), 3.71 (t, 2H, J=5.86 Hz), 2.26 (s, 3H), 1.86 (m, 2H); 19F-NMR (376 MHz, (CD3)2CO) δ −108.14; MS 445.1 m/z (AP+), 443.1 m/z (AP−). Anal. Calcd. for C17H18FIN2O3: C, 45.96; H,L 4.08; N, 6.31; F, 4.28; I, 28.57. Found: C, 45.78; H, 3.88; N, 6.14; F, 4.30; I, 28.27.

후처리

  1. stirringAfter 2 h of stirring
  2. extractionThe aqueous layer was extracted with ethyl acetate (1×20 mL, 2×10 mL)
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe resultant mixture was filtered
  6. customthe filtrate solvent was removed in vacuo
  7. customto obtain an oil that
  8. customwas dried on a vacuum pump over the weekend
  9. customThe oil was purified by flash chromatography
  10. washeluted with a gradient of 100% hexanes to 100% ethyl acetate in 50 min
  11. customThe solvent was removed in vacuo of combined fractions
  12. customto obtain a solid which
  13. customwas dried on a vacuum pump for c
  14. custom6 h
  15. customRecrystalized solid
  16. additionin a mixture of hexanes and ethyl acetate

출처 및 근거

ORD 기록
ord-13496b5f05e24476982b0074bf911b54
출처 데이터셋
uspto-grants-2005_11
특허 번호
US06960614B2

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