1-Bromo-3-chloropropane → HCID 17956069, 화합물

HRID 2102634노트

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HRID 2102634 반응식
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]=[CH:5]2.[H-].[Na+].Br[CH2:16][CH2:17][CH2:18]Cl.C([O-])([O-])=O.[K+].[K+].[CH2:26]([CH:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)[CH2:27][CH2:28][CH3:29]>CCOCC.CC#N.CCOC(C)=O.CN(C=O)C>[CH2:26]([CH:30]1[CH2:35][CH2:34][N:33]([CH2:16][CH2:17][CH2:18][N:8]2[C:9]3[C:4](=[CH:3][C:2]([Cl:1])=[CH:11][CH:10]=3)[CH:5]=[CH:6][C:7]2=[O:12])[CH2:32][CH2:31]1)[CH2:27][CH2:28][CH3:29]

참가 물질

10

반응물 5

HCID 80061-Bromo-3-chloropropaneHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 3266466-Chloro-2-hydroxyquinolineHCID 132838674-Butylpiperidine

생성물 1

HCID 17956069HCID 17956069, 화합물수율 49,444.398%

시약·촉매·용매 4

HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

A 4 mL vial was charged with 6-chloro-1H-quinolin-2-one (107LH35) (0.085 g, 0.47 mmol), dry DMF (3 mL) and NaH (60% in oil, 0.023 g, 0.56 mmol) and the mixture was stirred at rt for 45 min under a N2 atmosphere. Thereafter, 1-bromo-3-chloropropane (18 μl, 0.18 mmol) was added and the mixture was shaken at rt overnight, the reaction diluted with ether (25 mL) and washed with water (15 mL). The ether phase was washed with brine (15 mL), dried over Na2SO4, concentrated under reduced pressure. The oily residue was diluted with dry CH3CN (2 mL) and KI (0.170 g, 1.0 mmol), K2CO3 (0.140 g, 1.0 mmol) and 4-butylpiperidine (0.071 g, 0.50 mmol) were added. The mixture was shaken at 50° C. for 24 h and then diluted with EtOAc (25 mL) and washed with water (15 mL). The water phase was extracted (2×25 mL) and the combined organic phases were dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by prep RP-HPLC to give the title compound (32 mg, 89 mmol, 19%). 1H NMR (CD3OD) δ 7.80 (d, J=9.2 Hz, 1H), 7.66 (brs, 1H), 7.60-7.51 (m, 2H), 6.65 (d, J=9.6 Hz, 1H), 5.30 (t, J=7.6 Hz, 2H), 3.09-2.95 (m, 2H), 2.68-2.57 (m, 2H), 2.24-2.06 (m 2H), 2.00-1.90 (m, 2H), 1.75-1.64 (m, 2H), 1.32-1.12 (m, 9H), 0.84 (t, 6.4 Hz, 3H); 13C NMR (CD3OD) δ 162.6, 139.2, 137.4, 130.8, 128.0, 127.8, 122.4, 121.5, 116.3, 55.0, 53.3, 40.3, 35.7, 34.8, 31.0, 28.6, 23.9, 22.5, 13.0; HPLC-MS (ammonium acetate) [M+H]+=361.3.

후처리

  1. stirringthe mixture was shaken at rt overnight
  2. washwashed with water (15 mL)
  3. washThe ether phase was washed with brine (15 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. additionwere added
  7. stirringThe mixture was shaken at 50° C. for 24 h
  8. washwashed with water (15 mL)
  9. extractionThe water phase was extracted (2×25 mL)
  10. dry with materialthe combined organic phases were dried over Na2SO4
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by prep RP-HPLC

출처 및 근거

ORD 기록
ord-b3cff015d680486c8da2fd073f0fb0c1
출처 데이터셋
uspto-grants-2009_08
특허 번호
US07576078B2

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