Ethyl Acetate → 10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-chromeno[3,4-f]quinolin-5-ol

HRID 1838673

反応式

HRID 1838673 の反応式
[CH3:1][O:2][C:3]1[C:4]2[C:20]3[C:11](=[C:12]4[C:17](=[CH:18][CH:19]=3)[NH:16][C:15]([CH3:22])([CH3:21])[CH:14]=[C:13]4[CH3:23])[C:10](=[O:24])[O:9][C:5]=2[CH:6]=[CH:7][CH:8]=1.CC(C[AlH]CC(C)C)C.CCOC(C)=O.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C(Cl)Cl.CCCCCCC>[CH3:1][O:2][C:3]1[C:4]2[C:20]3[C:11](=[C:12]4[C:17](=[CH:18][CH:19]=3)[NH:16][C:15]([CH3:21])([CH3:22])[CH:14]=[C:13]4[CH3:23])[CH:10]([OH:24])[O:9][C:5]=2[CH:6]=[CH:7][CH:8]=1

参加物

7

反応物 4

HCID 8857Ethyl AcetateHCID 9357Potassium Sodium TartrateHCID 14487Diisobutylaluminum hydrideHCID 1091421810-methoxy-2,2,4-trimethyl-1,2-dihydro-5H-chromeno[3,4-f]quinolin-5-one

生成物 1

HCID 1108859510-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-chromeno[3,4-f]quinolin-5-ol収率 79.9%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8900Heptane溶媒

実験手順

The product from Example 5 (75.2g, 98% potent, 0.23 mol) in CH2Cl2 (3.8 L) under N2 was cooled to −78° C. and treated with 1M DIBAL in heptane (328 ml) dropwise over 1-1.5 hours while maintaining the temperature below −76° C. The reaction was monitored by HPLC and/or TLC until the reaction was complete (1.5 hours). EtOAc (1 L) and a saturated Rochelle salt solution (2 L) was added. The mixture was allowed to warmed to room temperature and stirring was continued until the organic and aqueous layers clearly separated. The organic layer was then washed with brine (0.5L), dried over Na2SO4 and concentrated to a thick suspension (approx. 300 g). The suspension was then cooled to 0° C., filtered and washed with cold EtOAc. The wet cake was dried under reduced pressure at 40° C. to provide the title compound (59.4 g, 99% potent, 80% potency adjusted yield). A small reference sample was recrystallized from EtOAc. mp 184-5° C.; Anal. Calcd for C20H21NO3: C, 74.28; H, 6.55; N, 4.33. Found C, 73.32; H, 6.51; N, 4.24. 1H NMR [(CD3)2SO] δ1.08 (3H, s), 1.26 (3H, s), 2.23 (3H, s), 3.86 (3H, s), 5.42 (1H, s), 6.11 (1H, s), 6.56 (1H, d), 6.61 (1H, d), 6.64 (1H, d), 6,71 (1H, d), 6.94 (1H, d), 7.07 (1H, t), 7.99 (1H, d); 13C NMR [(CD3)2SO] δ22.8, 28.1, 29.9, 49.6, 55.6, 89.8, 105.4, 110.8, 113.0, 113.9, 116.2, 117.0, 126.6, 127.2, 128.2, 130.0, 132.5, 145.4, 150.5, 156.5; FAB HRMS: calcd for C20H21NO3: 323.1521. Observed 323.1514.

後処理

  1. temperaturewhile maintaining the temperature below −76° C
  2. custom(1.5 hours)
  3. customclearly separated
  4. washThe organic layer was then washed with brine (0.5L)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to a thick suspension (approx. 300 g)
  7. temperatureThe suspension was then cooled to 0° C.
  8. filtrationfiltered
  9. washwashed with cold EtOAc
  10. customThe wet cake was dried under reduced pressure at 40° C.

出典と根拠

ORDレコード
ord-c7647777126e417da7a00b4678283db6
出典データセット
uspto-grants-2004_01
特許番号
US06673930B2

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