Ethyl Acetate → Jnj-18038683

HRID 2106372ノート

反応式

HRID 2106372 の反応式
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

参加物

10

反応物 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

生成物 1

HCID 11249539Jnj-18038683収率 92%

試薬・触媒・溶媒 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 1140Toluene溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-f1038ca7a8f643238d589d187787f8cb
出典データセット
uspto-grants-2009_08
特許番号
US07579470B2

反応ノート

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