Water → (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 391762노트

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HRID 391762 반응식
[CH3:1][O:2][C:3]([CH: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].[Cl:24][C:25]1[CH:26]=[C:27]([CH:39]=[CH:40][C:41]=1[Cl:42])[CH2:28][O:29][C:30]1[CH:35]=[CH:34][C:33]([C:36](=[O:38])[CH3:37])=[CH:32][CH:31]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[CH3:1][O:2][C:3]([CH:5]1[CH2:14][C:13]2[CH:12]=[C:11]3[O:15][CH2:37][C@@:36]([C:33]4[CH:34]=[CH:35][C:30]([O:29][CH2:28][C:27]5[CH:39]=[CH:40][C:41]([Cl:42])=[C:25]([Cl:24])[CH:26]=5)=[CH:31][CH:32]=4)([OH:38])[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

6

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27750311-(4-((3,4-Dichlorobenzyl)oxy)phenyl)ethanoneHCID 667196016,7-Dihydroxy-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester 3-methyl ester

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 63.5%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
100 °C

실험 절차

6,7-Dihydroxy-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester 3-methyl ester (0.76 g) was dissolved in anhydrous DMF (20 mL). To this solution 1-[4-(3,4-dichloro-benzyloxy)-phenyl]-ethanone (0.93 g) and potassium carbonate (0.7 g) were added and heated to 100° C. The reaction mixture was stirred at this temperature for 12 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate (50 mL) and washed with brine (2×50 mL), dried over (sodium sulfate) and concentrated in vacuo to give the crude product. The residue was then purified by flash column chromatography (hexanes:ethyl acetate 90:10 to 60:40) to give the desired product, (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 (0.92 g). 1H NMR (400 MHz, CDCl3): 7.91 (d, 2H), 7.82 (d, 1H), 7.58 (d, 1H), 7.54 (d, 1H), 7.47 (m, 1H), 7.00 (m, 2H), 6.78 (m, 1H), 5.32 (s, 1H), 5.09 (s, 2H), 4.70 (m, 1H), 4.40 (m, 1H), 3.62 (s, 3H), 3.06 (m, 1H), 1.51 (s, 9H), 1.26 (m, 2H), and 0.88 (t, 2H).

후처리

  1. extractionextracted with ethyl acetate (50 mL)
  2. washwashed with brine (2×50 mL)
  3. dry with materialdried over (sodium sulfate)
  4. concentrationconcentrated in vacuo
  5. customto give the crude product
  6. customThe residue was then purified by flash column chromatography (hexanes:ethyl acetate 90:10 to 60:40)

출처 및 근거

ORD 기록
ord-6314167919674194a6aabf978ff17f39
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08383644B2

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