Lithium hydroxide, monohydrate → US10188653, Example 2

HRID 59910Notes

Reaction equation

HRID 59910 reaction equation
[CH2:1]([O:3][C:4]1[CH:38]=[CH:37][CH:36]=[CH:35][C:5]=1[O:6][C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]2[N:18]=[CH:17][C:16]([C:19]([NH:21][CH2:22][C:23]3[CH:24]=[C:25]([CH:30]=[C:31]([O:33][CH3:34])[CH:32]=3)[C:26]([O:28]C)=[O:27])=[O:20])=[CH:15][N:14]=2)[CH2:8]1)[CH3:2].O[Li].O>C1COCC1.O>[CH2:1]([O:3][C:4]1[CH:38]=[CH:37][CH:36]=[CH:35][C:5]=1[O:6][C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]2[N:14]=[CH:15][C:16]([C:19]([NH:21][CH2:22][C:23]3[CH:24]=[C:25]([CH:30]=[C:31]([O:33][CH3:34])[CH:32]=3)[C:26]([OH:28])=[O:27])=[O:20])=[CH:17][N:18]=2)[CH2:8]1)[CH3:2]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 131737072methyl (R)-3-((2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)methyl)-5-methoxybenzoate

Product 1

HCID 118366225US10188653, Example 2Yield 72%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a solution of methyl (R)-3-((2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)methyl)-5-methoxybenzoate (60 mg, 0.11 mmol) in THF:H2O (1:1, 5 mL) at 20-25° C. was added LiOH.H2O (15 mg, 0.34 mmol). The mixture was stirred for 18 hours, and then was concentrated under reduced pressure. The resulting residue was diluted with water (5 mL) and washed with ethyl acetate (3 times with 5 mL). The aqueous layer was acidified to pH 2 with 1N HCl (5 mL), and then was extracted with ethyl acetate (3 times with 5 mL). The combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure to afford (R)-3-((2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)methyl)-5-methoxybenzoic acid (40 mg, 72%). 1H NMR (300 MHz, DMSO-d6) δ 8.91 (m, 1H), 8.78 (s, 2H), 7.49 (s, 1H), 7.34 (s, 1H), 7.02 (m, 2H), 6.89 (m, 3H), 4.45 (d, 2H), 4.32 (m, 1H), 4.20 (d, 1H), 3.91 (m, 5H), 3.78 (s, 3H), 2.05 (m, 1H), 1.85 (m, 2H), 1.52 (m, 1H), 1.21 (t, 3H). MS (ES+) 507.1 (M+H).

Workup

  1. concentrationwas concentrated under reduced pressure
  2. additionThe resulting residue was diluted with water (5 mL)
  3. washwashed with ethyl acetate (3 times with 5 mL)
  4. extractionwas extracted with ethyl acetate (3 times with 5 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1aa5ad4321494b98bf12b0cf15bba8e3
Source dataset
uspto-grants-2016_09
Patent number
US09440949B2

Reaction notes

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