Methanol → HCID 67408933, compound

HRID 1802092Notes

Reaction equation

HRID 1802092 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]=[C:14]([C@H:19]([CH3:22])[CH2:20][OH:21])[N:13]=[CH:12]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].C(Cl)Cl.ClC(Cl)(Cl)[C:28]([N:30]=C=O)=[O:29].CO.C(=O)([O-])[O-].[K+].[K+].O>>[C:28](=[O:29])([O:21][CH2:20][C@H:19]([C:14]1[N:13]=[CH:12][C:11]2[C:16](=[CH:17][CH:18]=[C:9]([O:8][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])[CH:10]=2)[N:15]=1)[CH3:22])[NH2:30]

Participants

7

Reactant 6

HCID 887MethanolHCID 962WaterHCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 76400Trichloroacetyl isocyanateHCID 67408545HCID 67408545, compound

Product 1

HCID 67408933HCID 67408933, compound

Conditions

Temperature
23 °C

Procedure

(S)-2-(6-Heptyloxy-quinazolin-2-yl)-propan-1-ol (13, 950 mg, 0.0031 mol) was dissolved in methylene chloride (100 mL, 2 mol), followed by trichloroacetyl isocyanate (449 μL, 0.00377 mol) dropwise at 0° C. The reaction mixture was then gradually warmed up to 23° C., and stirred for additional for 1 hour. Solvent was removed under vacuum, and the residue was redissolved in methanol (100 mL, 3 mol), followed by potassium carbonate (5000 mg, 0.03 mol) and water (20 mL, 1 mol) at 0° C. The reaction mixture was then warmed up to at 23° C. and stirred for 3 hours. MeOH was removed under vacuum, and the aqueous layer was treated with DCM (10×5 mL). The combined organic layers were then washed with water and brine, and then dried over Na2SO4. The crude mixture was purified via chromatography (SiO2, 4 g, 0-100% ethyl acetate/hexanes) to give 1.05 g, (97%). 1H NMR (400 MHz, CHLOROFORM-d) δ: 9.24 (s, 1H), 7.89 (d, J=9.3 Hz, 1H), 7.53 (dd, J=9.0, 2.8 Hz, 1H), 7.11 (d, J=2.8 Hz, 1H), 4.60 (dd, J=10.5, 8.0 Hz, 1H), 4.51 (br. s., 2H), 4.45 (dd, J=10.5, 6.0 Hz, 1H), 4.09 (t, J=6.5 Hz, 2H), 3.47-3.62 (m, 1H), 1.81-1.92 (m, 2H), 1.40-1.65 (m, 11H), 0.82-0.96 (m, 3H). MS (ES, M+1): 346.30.

Workup

  1. customSolvent was removed under vacuum
  2. temperatureThe reaction mixture was then warmed up to at 23° C.
  3. stirringstirred for 3 hours
  4. customMeOH was removed under vacuum
  5. additionthe aqueous layer was treated with DCM (10×5 mL)
  6. washThe combined organic layers were then washed with water and brine
  7. dry with materialdried over Na2SO4
  8. customThe crude mixture was purified via chromatography (SiO2, 4 g, 0-100% ethyl acetate/hexanes)
  9. customto give 1.05 g, (97%)

Sources & evidence

ORD record
ord-7691d7818940475781f8607797e6c0d1
Source dataset
uspto-grants-2013_01
Patent number
US08349849B2

Reaction notes

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