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

HRID 1469169Notes

Reaction equation

HRID 1469169 reaction equation
[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]

Participants

5

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-9f2fcb60d76a45a08f5baf65e42ab30f
Source dataset
uspto-grants-2015_04
Patent number
US09006242B2

Reaction notes

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