tert-Butanol → HCID 178445794, compound

HRID 1802102Notes

Reaction equation

HRID 1802102 reaction equation
[OH:1][C:2]1[C:3]([I:19])=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C@:12]1([CH3:18])[CH2:16][O:15][C:14](=[O:17])[NH:13]1)[N:6]=[CH:5]2.[C:20]([CH:24]1[CH2:29][CH2:28][CH:27](OS(C)(=O)=O)[CH2:26][CH2:25]1)([CH3:23])([CH3:22])[CH3:21].C(=O)([O-])[O-].[Cs+].[Cs+].C(O)(C)(C)C.CC(=O)CC>C(Cl)Cl>[C:20]([C@H:24]1[CH2:29][CH2:28][C@H:27]([O:1][C:2]2[C:3]([I:19])=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[C:7]([C@:12]2([CH3:18])[CH2:16][O:15][C:14](=[O:17])[NH:13]2)[N:6]=[CH:5]3)[CH2:26][CH2:25]1)([CH3:23])([CH3:22])[CH3:21]

Participants

7

Reactant 5

HCID 6386tert-ButanolHCID 6569Methyl Ethyl KetoneHCID 10796Cesium carbonateHCID 11128255Methanesulfonic acid 4-tert-butyl-cyclohexyl ester2×HCID 67409863(R)-4-(6-Hydroxy-5-iodoquinazolin-2-yl)-4-methyloxazolidin-2-one

Product 1

HCID 178445794HCID 178445794, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

(R)-4-(6-Hydroxy-5-iodo-quinazolin-2-yl)-4-methyl-oxazolidin-2-one (350.0 mg, 0.0009431 mol), methanesulfonic acid 4-tert-butyl-cyclohexyl ester (884.0 mg, 0.003772 mol) and cesium carbonate (921.8 mg, 0.002829 mol) were dissolved in a mixture of tert-butyl alcohol (19.9 mL, 0.208 mol) and 2-butanone (6.6 mL, 0.074 mol). The reaction mixture was heated at 80° C. for 1 hour (MW), an additional methanesulfonic acid 4-tert-butyl-cyclohexyl ester (500 mg) was added, and the mixture was heated at 80° C. for an additional for 1 hour. LC/MS indicated that reaction was completed. Removal of solvents gave a solid mixture, which was treated with DCM and filtered. The filtrate was then washed with water, brine and dried over Na2SO4. The crude mixture was then purified via chromatography (SiO2, 24 gm, 0-100% ethyl acetate/hexanes) to give 451 mg desired product (94%).1H NMR (CHLOROFORM-d) δ: 9.55 (s, 1H), 7.94 (d, J=9.3 Hz, 1H), 7.61 (d, J=9.3 Hz, 1H), 6.07 (s, 1H), 5.16 (d, J=8.8 Hz, 1H), 4.50 (d, J=8.8 Hz, 1H), 4.24-4.42 (m, 1H), 2.24 (d, J=12.0 Hz, 2H), 1.92 (d, J=9.5 Hz, 2H), 1.76 (s, 3H), 1.63 (d, J=11.3 Hz, 1H), 1.22-1.39 (m, 2H), 1.15 (br. s., 2H), 0.81-0.98 (m, 9H). MS (M+1): 510.10.

Workup

  1. temperaturethe mixture was heated at 80° C. for an additional for 1 hour
  2. customLC/MS indicated that reaction
  3. customRemoval of solvents
  4. customgave a solid mixture, which
  5. filtrationfiltered
  6. washThe filtrate was then washed with water, brine
  7. dry with materialdried over Na2SO4
  8. customThe crude mixture was then purified via chromatography (SiO2, 24 gm, 0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4812dd6496b74c87b23405a9ad110c81
Source dataset
uspto-grants-2013_01
Patent number
US08349849B2

Reaction notes

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