Water → HCID 10138368, compound

HRID 1062288Notes

Reaction equation

HRID 1062288 reaction equation
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

Participants

5

Reactant 3

HCID 962WaterHCID 1118Sulfuric Acid2×HCID 22286093HCID 22286093, compound

Product 1

HCID 10138368HCID 10138368, compoundYield 74.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-13496b5f05e24476982b0074bf911b54
Source dataset
uspto-grants-2005_11
Patent number
US06960614B2

Reaction notes

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