Acetic Acid → HCID 86732760, 화합물

HRID 525894노트

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HRID 525894 반응식
[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)=[C:10]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:11]=2[F:13])[C:6](=[O:34])[C:5]([CH:35]=O)=[CH:4]1)[CH3:2].[NH:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CC(O)=O>ClCCCl.C(Cl)Cl>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([O:24][CH2:25][C:26]3[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=3)=[C:10]([O:14][CH2:15][C:16]3[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=3)[C:11]=2[F:13])[C:6](=[O:34])[C:5]([CH2:35][N:37]2[CH2:41][CH2:40][CH2:39][CH2:38]2)=[CH:4]1)[CH3:2]

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 86732759HCID 86732759, 화합물

생성물 1

HCID 86732760HCID 86732760, 화합물수율 59.5%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 6344Dichloromethane용매

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온도
25 °C

실험 절차

To a solution of 1-ethyl-8-fluoro-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carbaldehyde (6.5 g, 13.22 mmol) in 1,2-Dichloroethane (DCE) (100 mL) was added pyrrolidine (1.637 mL, 19.84 mmol), sodium triacetoxyborohydride (5.61 g, 26.4 mmol) and AcOH (0.076 mL, 1.322 mmol). The reaction mixture was stirred at 25° C. for 3 h. LCMS indicated completion of the reaction. The mixture was diluted with DCM and washed with brine. The organic layer was dried over sodium sulfate and evaporated in vacuo. The crude material was purified by normal phase automatic silica column chromatography (Combiflash RF, 40 g golden column) eluting with MeOH/DCM (0-20%), and purified again with reverse phase automatic silica column chromatography (Combiflash RF, 150 g golden column) eluting with acetonitrile/Water (0-60%) to afford 1-ethyl-8-fluoro-6,7-bis((4-methoxybenzyl)oxy)-3-(pyrrolidin-1-ylmethyl)quinolin-4(1H)-one (4.3 g, 7.87 mmol, 59.5% yield) as a pale yellow solid.

후처리

  1. customcompletion of the reaction
  2. washwashed with brine
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. customevaporated in vacuo
  5. customThe crude material was purified by normal phase automatic silica column chromatography (Combiflash RF, 40 g golden column)
  6. washeluting with MeOH/DCM (0-20%)
  7. custompurified again with reverse phase automatic silica column chromatography (Combiflash RF, 150 g golden column)
  8. washeluting with acetonitrile/Water (0-60%)

출처 및 근거

ORD 기록
ord-07933e7f32244731bdda980a73a5e4d6
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340556B2

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