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

HRID 1059125Notes

Reaction equation

HRID 1059125 reaction equation
[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8900HeptaneSolvent

Procedure

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] δ 1.08 (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), 3C NMR [(CD3)2SO] δ 22.8, 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.

Workup

  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.

Sources & evidence

ORD record
ord-4e2fc0b63bd746029ff704c8b8291e06
Source dataset
uspto-grants-2003_02
Patent number
US06518430B1

Reaction notes

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