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

HRID 1469169노트

반응식

HRID 1469169 반응식
[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]

참가 물질

5

반응물 2

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

생성물 1

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

시약·촉매·용매 2

HCID 702Ethanol용매HCID 962Water용매

반응 조건

온도
60 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-9f2fcb60d76a45a08f5baf65e42ab30f
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09006242B2

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