Sodium Hydroxide → 5-((1-(tert-Butoxycarbonyl)piperidin-4-yl)ethynyl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzoic acid

HRID 1469169ノート

反応式

HRID 1469169 の反応式
[CH2:1]([N:3]([CH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1)[C:4]1[CH:5]=[C:6]([C:15]#[C:16][CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)[CH:7]=[C:8]([C:11]([O:13]C)=[O:12])[C:9]=1[CH3:10])[CH3:2].[OH-].[Na+]>C(O)C.O>[C:26]([O:25][C:23]([N:20]1[CH2:21][CH2:22][CH:17]([C:16]#[C:15][C:6]2[CH:5]=[C:4]([N:3]([CH2:1][CH3:2])[CH:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[C:9]([CH3:10])=[C:8]([CH:7]=2)[C:11]([OH:13])=[O:12])[CH2:18][CH2:19]1)=[O:24])([CH3:28])([CH3:29])[CH3:27]

参加物

5

反応物 2

HCID 14798Sodium HydroxideHCID 86715574tert-Butyl 4-((3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-5-(methoxycarbonyl)-4-methylphenyl)ethynyl)piperidine-1-carboxylate

生成物 1

HCID 867155755-((1-(tert-Butoxycarbonyl)piperidin-4-yl)ethynyl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzoic acid収率 99%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 962Water溶媒

反応条件

温度
60 °C

実験手順

To a solution of tert-butyl 4-((3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-5-(methoxycarbonyl)-4-methylphenyl)ethynyl)piperidine-1-carboxylate (2.4 g, 4.95 mmol) in ethanol (20.0 mL) was added a solution of sodium hydroxide (0.565 g, 14.1 mmol) in water (3.0 ml) at rt. The reaction mixture was heated at 60° C. for 6 h. The reaction was quenched with 1M HCl (5 mL) and then excess citric acid solution to adjust to the pH to 5. The mixture was concentrated to remove EtOH and the remaining aqueous phase was extracted with AcOEt (2×40 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The residue was purified by chromatography (10%-100% AcOEt/Heptane) to give the titled compound (2.30 g, 99% yield). 1H-NMR (500 MHz) δ ppm; 7.82 (s, 1H), 7.35 (s, 1H), 3.98 (brd, J=11.3 Hz, 2H), 3.77 (m, 2H), 3.35 (dt, J=1.5, 11.3 Hz, 2H), 3.25 (ddd, J=3.4, 8.3, 12.2 Hz, 2H), 3.11 (brs, 2H), 3.00 (brs, 1H), 2.81 (dddd, J=3.9, 3.9, 3.9, 3.9 Hz, 1H), 2.60 (s, 3H), 1.88 (m, 2H), 1.60-1.78 (m, 6H), 1.48 (s, 9H), 0.90 (t, J=6.8 Hz, 3H); MS (ESI) [M+H]+471.4.

後処理

  1. customThe reaction was quenched with 1M HCl (5 mL)
  2. concentrationThe mixture was concentrated
  3. customto remove EtOH
  4. extractionthe remaining aqueous phase was extracted with AcOEt (2×40 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography (10%-100% AcOEt/Heptane)

出典と根拠

ORDレコード
ord-9f2fcb60d76a45a08f5baf65e42ab30f
出典データセット
uspto-grants-2015_04
特許番号
US09006242B2

反応ノート

読み込み中…