tert-Butanol → HCID 178445794、化合物

HRID 709886ノート

反応式

HRID 709886 の反応式
[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]

参加物

7

反応物 5

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

生成物 1

HCID 178445794HCID 178445794、化合物収率 94%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
80 °C

実験手順

(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.

後処理

  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)

出典と根拠

ORDレコード
ord-29b309e65c664c08ba4dc135684ac426
出典データセット
uspto-grants-2015_11
特許番号
US09181191B2

反応ノート

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