Sodium Bicarbonate → Methyl 2-fluoro-5-[{4-[(4-fluorophenyl)ethynyl]benzyl)-(hexyl)amino]benzoate

HRID 551967ノート

反応式

HRID 551967 の反応式
[F:1][C:2]1[CH:11]=[CH:10][C:9]([NH:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]#[C:27][C:28]2[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=2)=[CH:22][CH:21]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[F:1][C:2]1[CH:11]=[CH:10][C:9]([N:12]([CH2:32][C:31]2[CH:30]=[CH:29][C:28]([C:27]#[C:26][C:23]3[CH:22]=[CH:21][C:20]([F:19])=[CH:25][CH:24]=3)=[CH:35][CH:34]=2)[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

参加物

6

反応物 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 43715358Methyl 2-fluoro-5-(hexylamino)benzoateHCID 454901144-[2-(4-Fluorophenyl)ethynyl]benzaldehyde

生成物 1

HCID 57554486Methyl 2-fluoro-5-[{4-[(4-fluorophenyl)ethynyl]benzyl)-(hexyl)amino]benzoate収率 32%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

反応条件

温度
50 °C

実験手順

To a solution of methyl 2-fluoro-5-(hexylamino)benzoate (270 mg; 1.07 mmol) and 4-[(4-fluorophenyl)ethynyl]benzaldehyde (358 mg; 1.60 mmol, intermediate which may be obtained according to methods disclosed in EP03103780.7) in anhydrous DCE (15 mL) was added sodium triacetoxyborohydride (678 mg; 3.20 mmol) at rt. The reaction mixture was then heated at 50° C. for 14 h. It was then poured into a solution of saturated NaHCO3 and extracted twice with DCM. The combined organic phases were then washed with brine, dried over MgSO4, filtrated and concentrated. The crude brown oil (652 mg) was purified by preparative HPLC using a X-Terra column to give 158 mg (32%) of the title compound as a beige powder. HPLC, Rt: 6.01 min (purity: 96.5%), LC/MS, M+(ESI): 462.2, 1H NMR: (CDCl3) δ: 7.46 (m, 2H), 7.41 (d, J=8.3 Hz, 2H), 7.37 (m, 1H), 7.13 (d, J=7.9 Hz, 2H), 6.94-7.05 (m, 4H), 4.52 (s, 2H), 3.90 (s, 3H), 3.42 (t, J=7.7 Hz, 2H), 1.56 (m, 2H), 1.26 (m, 6H), 0.85 (t, J=6.6 Hz, 3H).

後処理

  1. extractionextracted twice with DCM
  2. washThe combined organic phases were then washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltrated
  5. concentrationconcentrated
  6. customThe crude brown oil (652 mg) was purified by preparative HPLC

出典と根拠

ORDレコード
ord-bdbd0bd98cfe4bb886f4b6f6e72d5cc1
出典データセット
uspto-grants-2011_05
特許番号
US07947851B2

反応ノート

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