2-Methyl-1,2,3,4-tetrahydro-beta-carboline → 4-(2-Methyl-1,2,3,4-tetrahydro-b-carbolin-9-ylmethyl)benzoic acid methyl ester

HRID 403635ノート

反応式

HRID 403635 の反応式
[CH3:1][N:2]1[CH2:14][CH2:13][C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[NH:5][C:4]=2[CH2:3]1.CC(C)([O-])C.[K+].[CH3:21][O:22][C:23](=[O:32])[C:24]1[CH:29]=[CH:28][C:27]([CH2:30]Br)=[CH:26][CH:25]=1>>[CH3:21][O:22][C:23](=[O:32])[C:24]1[CH:29]=[CH:28][C:27]([CH2:30][N:5]2[C:4]3[CH2:3][N:2]([CH3:1])[CH2:14][CH2:13][C:12]=3[C:11]3[C:6]2=[CH:7][CH:8]=[CH:9][CH:10]=3)=[CH:26][CH:25]=1

参加物

4

反応物 3

HCID 1218962-Methyl-1,2,3,4-tetrahydro-beta-carbolineHCID 256687Methyl 4-(bromomethyl)benzoateHCID 23665647Potassium tert-butoxide

生成物 1

HCID 668732554-(2-Methyl-1,2,3,4-tetrahydro-b-carbolin-9-ylmethyl)benzoic acid methyl ester収率 33.2%

反応条件

温度
120 °C

実験手順

A round bottom flask fitted with reflux condenser containing 2-methyl-2,3,4,9-tetrahydro-1H-b-carboline (16) (0.30 g, 1.62 mmol) and potassium tert-butoxide (0.22 g, 1.92 mmol) was vacuum purged and filled with argon, followed by addition of DMSO (5 mL). After stirring at 120° C. for 20 min, 4-bromomethyl-benzoic acid methyl ester (0.37 g, 1.62 mmol) was added and the mixture was stirred at 120° C. for 3 h. The reaction was quenched by addition of water (30 mL), transferred to a separatory funnel and extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine (2×20 mL), dried (Na2SO4) and concentrated. The product was purified by MPCC (0 to 5% gradient of MeOH in CH2Cl2), which gave 180 mg (33%) of the title compound. 1H NMR (400 MHz, CDCl3): δ 7.95 (d, 2H, J=8.2 Hz), 7.54 (m, 1H, J=7.6 Hz), 7.18-7.11 (m, 4H), 7.15 (d, 2H, J=8.1 Hz), 5.25 (s, 2H), 3.89 (s, 3H), 3.53 (s, 2H), 2.90 (m, 2H), 2.80 (m, 2H), 2.51 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 166.5, 141.9, 137.4, 130.4, 126.0, 122.8, 120.2, 118.6, 109.4, 106.7, 52.2, 51.3, 49.7, 46.6, 45.56, 42.1, 18.5. ESI-HRMS (m/z): [M+H]+ calcd. for C21H22N2O2, 335.1727. found, 335.1724.

後処理

  1. customA round bottom flask fitted
  2. temperaturewith reflux condenser
  3. custompurged
  4. additionfilled with argon
  5. additionfollowed by addition of DMSO (5 mL)
  6. stirringthe mixture was stirred at 120° C. for 3 h
  7. customThe reaction was quenched by addition of water (30 mL)
  8. customtransferred to a separatory funnel
  9. extractionextracted with ethyl acetate (3×20 mL)
  10. washThe combined organic layers were washed with brine (2×20 mL)
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated
  13. customThe product was purified by MPCC (0 to 5% gradient of MeOH in CH2Cl2), which

出典と根拠

ORDレコード
ord-0848d7242af84127a8787d8545477803
出典データセット
uspto-grants-2014_06
特許番号
US08748451B2

反応ノート

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