Dichloromethane → 4-(7-fluoro-3-methoxycarbonylmethyl-naphthalen-1-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 2363812노트

반응식

HRID 2363812 반응식
C(=O)([O-])[O-].[K+].[K+].[CH3:7][O:8][C:9](=[O:30])[CH2:10][C:11]1[CH:20]=[C:19](OS(C(F)(F)F)(=O)=O)[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([F:29])[CH:17]=2)[CH:12]=1.[C:31]([O:35][C:36]([N:38]1[CH2:43][CH:42]=[C:41](B2OC(C)(C)C(C)(C)O2)[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].ClCCl>CN(C=O)C.CO.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].C(OCC)(=O)C>[C:31]([O:35][C:36]([N:38]1[CH2:39][CH:40]=[C:41]([C:19]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([F:29])[CH:17]=3)[CH:12]=[C:11]([CH2:10][C:9]([O:8][CH3:7])=[O:30])[CH:20]=2)[CH2:42][CH2:43]1)=[O:37])([CH3:34])([CH3:32])[CH3:33]

참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 59326501(6-Fluoro-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl ester

생성물 1

HCID 866868854-(7-fluoro-3-methoxycarbonylmethyl-naphthalen-1-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester수율 54.2%

시약·촉매·용매 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 8857Ethyl Acetate용매HCID 21901440N,N-dimethylformamide methanol용매

실험 절차

Anhydrous potassium carbonate (0.40 g, 2.9 mmol) was added to a stirred solution of compound (6-fluoro-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl ester (which may be prepared as described above; 0.37 g, 1 mmol) and 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.30 g, 0.97 mmol) in dry DMF-MeOH (4:1, 5 mL) in a pressure tube. The mixture was deoxygenated by bubbling with argon for 15 min. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (available from Sigma-Aldrich; 80 mg, 0.1 mmol) was added under argon. The mixture was heated at reflux for 12 h and then cooled. Ethyl acetate (20 mL) was added and the mixture was filtered through a pad of celite. The celite was washed with ethyl acetate and the combined filtrates were concentrated under reduced pressure. The residue was purified by silica gel column chromatography (100-200 mesh), using 5% ethyl acetate/hexanes as eluent, to give 4-(7-fluoro-3-methoxycarbonylmethyl-naphthalen-1-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.21 g, 54%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 7.78 (dd, J=6.6, 4.4 Hz, 1H), 7.64 (s, 1H), 7.51 (dd, J=7.1, 1.1 Hz, 1H), 7.21-7.26 (m, 2H), 5.77 (s, 1H), 4.12 (s, 2H), 3.70-3.76 (m, 7H), 2.45-2.50 (m, 2H), 1.52 (m, 9H); MS cald. for C23H27FNO4 [(M+H)+] 400, obsd. 400.2.

후처리

  1. customThe mixture was deoxygenated
  2. additionwas added under argon
  3. temperatureThe mixture was heated
  4. temperatureat reflux for 12 h
  5. temperaturecooled
  6. filtrationthe mixture was filtered through a pad of celite
  7. washThe celite was washed with ethyl acetate
  8. concentrationthe combined filtrates were concentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (100-200 mesh)

출처 및 근거

ORD 기록
ord-cf3a9a09d18c49dea9a619284be3f0e2
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08691993B2

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