Ethyl Acetate → Jnj-18038683

HRID 2106372Notes

Reaction equation

HRID 2106372 reaction equation
C([O:5]C([N:8]1[CH2:17][CH2:16][C:15]2[N:14]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:13]=[C:12]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)[C:11]=2[CH2:10][CH2:9]1)=O)(C)(C)C.[C:32]([O-:35])([O-:34])=O.[Na+].[Na+].ClC1C=CC(B2[O:49][C:48]3[CH:50]=CC=C[C:47]=3[O:46]2)=CC=1.C(OC(N1CCC2N(CC3C=CC=CC=3)N=C(OS(C(F)(F)F)(=O)=O)C=2CC1)=O)(C)(C)C.CC[O:88][C:89]([CH3:91])=[O:90]>C1(C)C=CC=CC=1.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].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[C:89]([OH:88])(=[O:90])[CH2:91][C:48]([CH2:50][C:32]([OH:35])=[O:34])([C:47]([OH:46])=[O:5])[OH:49].[CH2:18]([N:14]1[C:15]2[CH2:16][CH2:17][NH:8][CH2:9][CH2:10][C:11]=2[C:12]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=2)=[N:13]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

10

Reactant 5

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 32553502-(4-Chlorophenyl)-1,3,2-benzodioxaboroleHCID 672688521-Benzyl-6-Boc-3-(4-chlorophenyl)-1,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepineHCID 865983901-benzyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester

Product 1

HCID 11249539Jnj-18038683Yield 92%

Reagents, catalysts & solvents 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

1-Benzyl-3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester. To a 1-L, three-necked, round-bottomed flask was added Pd(dppf)Cl2 (2.8 g, 3.4 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.96 g, 1.73 mmol), Bu4N+Br− (2.78 g, 8.6 mmol), Na2CO3 (36.5 g, 344 mmol) and 2-(4-chloro-phenyl)-benzo[1,3,2]dioxaborole (23.8 g, 103 mmol), under N2. A solution of 1-benzyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (41 g, 86 mmol) in toluene (250 mL) was added, followed by the addition of H2O (250 mL) via syringe. The reaction mixture was stirred at reflux for 3 h and then was cooled to rt. The organic layer was diluted with EtOAc (200 mL) and then was washed with 1 M aq. K2CO3 until the color of the aqueous layer stabilized. The organic layer was washed with brine (200 mL), dried over MgSO4, filtered, and concentrated. The crude product thus obtained was pad-filtered through a short plug of SiO2 to afford the title compound (34.5, 79 mmol, 92%) as a white solid. MS (ESI): exact mass calculated for C25H28ClN3O2, 437.19; found, m/z 438.1, [M+H]+. HPLC (Method B): Rt=10.89 min. 1H NMR (400 MHz, CDCl3): 7.50-7.45 (m, 2H), 7.40-7.36 (m, 2H), 7.36-7.25 (m, 3H), 7.13-7.10 (m, 2H), 5.35-5.33 (m, 2H), 3.56-3.50 (m, 4H), 2.83-2.75 (m, 4H), 1.28-1.25 (m, 9H).

Workup

  1. temperatureat reflux for 3 h
  2. washwas washed with 1 M aq. K2CO3 until the color of the aqueous layer
  3. washThe organic layer was washed with brine (200 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product thus obtained
  8. filtrationwas pad-filtered through a short plug of SiO2

Sources & evidence

ORD record
ord-f1038ca7a8f643238d589d187787f8cb
Source dataset
uspto-grants-2009_08
Patent number
US07579470B2

Reaction notes

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