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

HRID 2363812Notes

Reaction equation

HRID 2363812 reaction equation
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]

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolventHCID 21901440N,N-dimethylformamide methanolSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-cf3a9a09d18c49dea9a619284be3f0e2
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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