Potassium Carbonate → 4-(2-Cyclopropylmethyl-7-methyl-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 252067

반응식

HRID 252067 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[CH2:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].B1C2CCCC1CCC2.Br[C:25]1[CH:26]=[C:27]2[C:31](=[C:32]([CH3:34])[CH:33]=1)[C:30](=[O:35])[N:29]([CH2:36][CH:37]1[CH2:39][CH2:38]1)[CH2:28]2.C(=O)([O-])[O-].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:25]2[CH:26]=[C:27]3[C:31](=[C:32]([CH3:34])[CH:33]=2)[C:30](=[O:35])[N:29]([CH2:36][CH:37]2[CH2:39][CH2:38]2)[CH2:28]3)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

8

반응물 4

HCID 11430Potassium CarbonateHCID 789669-Borabicyclo(3.3.1)nonaneHCID 27568081-Boc-4-MethylenepiperidineHCID 579494565-Bromo-2-cyclopropylmethyl-7-methyl-2,3-dihydro-isoindol-1-one

생성물 1

HCID 576722654-(2-Cyclopropylmethyl-7-methyl-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester수율 68.9%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매2회HCID 6228Dimethylformamide용매

반응 조건

온도
60 °C

실험 절차

To a purged (Argon) sample of 4-Methylene-piperidine-1-carboxylic acid tert-butyl ester (727 mg, 3.68 mmol) was added 9-BBN (11.32 mL, 5.66 mmol). The mixture was stirred at 60° C. for two hours. After cooling to room temperature this solution was added to 5-Bromo-7-methyl-2-cyclopropylmethyl-2,3-dihydro-isoindol-1-one (794 mg, 2.83 mmol), Pd(dppf)Cl2 (115 mg, 0.142 mmol), DMF (25 mL), potassium carbonate (1.17 g, 8.49 mmol) and water (2.5 mL). The mixture was allowed to stir at 75° C. for 1.5 hours. The mixture was then cooled to room temperature and poured into water (3 mL). The product was extracted with ethyl acetate. The combined organic layers were washed with water three times, brine, dried over sodium sulphate, filtered and concentrated. Column chromatography (30% Ethyl acetate/hexanes) provided the title compound as a light yellow oil (777 mg, 53%). 1H NMR (300 MHz, CDCl3): δ 7.01 (s, 1H), 6.94 (s, 1H), 4.39 (s, 2H), 3.42 (d, 2H), 2.68 (s, 3H), 2.57 (s, 2H), 2.54 (d, 2H), 1.70-1.62 (m, 4H), 1.43 (s, 9H), 1.09 (d, 1H), 1.01 (m, 1H), 0.56-0.5 (m, 2H), 0.31-0.29 (m, 2H).

후처리

  1. temperatureAfter cooling to room temperature this solution
  2. stirringto stir at 75° C. for 1.5 hours
  3. temperatureThe mixture was then cooled to room temperature
  4. extractionThe product was extracted with ethyl acetate
  5. washThe combined organic layers were washed with water three times, brine
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-11f05c0702c74801b13b8d5fafe1bb66
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07868008B2

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