1,8-Diazabicyclo(5.4.0)undec-7-ene → (S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-3-hydroxy-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7,8-dicarboxylic acid 7-tert-butyl ester 8-methyl ester

HRID 879673노트

반응식

HRID 879673 반응식
[CH3:1][O:2][C:3]([C@@H:5]1[CH2:14][C:13]2[C:8](=[CH:9][C:10]([OH:16])=[C:11]([OH:15])[CH:12]=2)[CH2:7][N:6]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[O:4].Br[CH2:25][C:26]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[C:38]([Cl:43])[CH:37]=2)=[CH:30][CH:29]=1)=[O:27].C(=O)(O)[O-].[Na+].C1CCN2C(=NCCC2)CC1>CN(C=O)C.O.CCOC(C)=O>[CH3:1][O:2][C:3]([CH:5]1[CH2:14][C:13]2[CH:12]=[C:11]3[O:15][CH2:25][C@@:26]([C:28]4[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]5[CH:41]=[CH:40][C:39]([Cl:42])=[C:38]([Cl:43])[CH:37]=5)=[CH:30][CH:29]=4)([OH:27])[O:16][C:10]3=[CH:9][C:8]=2[CH2:7][N:6]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[O:4]

참가 물질

8

반응물 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 516892Sodium BicarbonateHCID 58327303(S)-6,7-dihydroxy-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester 3-methyl esterHCID 583275742-Bromo-1-[4-(3,4-dichloro-benzyloxy)-phenyl]-ethanone

생성물 1

HCID 66719236(S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-3-hydroxy-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7,8-dicarboxylic acid 7-tert-butyl ester 8-methyl ester수율 101.1%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

(S)-6,7-Dihydroxy-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester 3-methyl ester (30.0 g), 2-bromo-1-[4-(3,4-dichloro-benzyloxy)-phenyl]-ethanone (34.7 g), and sodium bicarbonate (7.8 g) were stirred together in 600 mL anhydrous DMF. While stirring at rt, DBU (6.95 mL) was added all at once and the mixture was stirred at rt for 18 hours. The reaction mixture was then poured into 1 L EtOAc and 500 mL water and the layers were separated. The organic layer was washed with water three times and brine once, then dried over sodium sulfate and concentrated to provide 57.8 g of orange foam which was used in the next step without further purification.

후처리

  1. stirringwas stirred at rt for 18 hours
  2. customthe layers were separated
  3. washThe organic layer was washed with water three times and brine once
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-912021f80a4e416482e270557bce68e5
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987295B2

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