Sodium Hydroxide → HCID 118366180, compound

HRID 59926Notes

Reaction equation

HRID 59926 reaction equation
[OH-].[Na+].[CH2:3]([O:5][C:6]1[CH:39]=[CH:38][CH:37]=[CH:36][C:7]=1[O:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:20]=[CH:19][C:18]([C:21]([NH:23][CH2:24][C:25]3[CH:26]=[C:27]([CH:32]=[C:33]([CH3:35])[CH:34]=3)[C:28]([O:30]C)=[O:29])=[O:22])=[CH:17][N:16]=2)[CH2:10]1)[CH3:4]>C1COCC1>[CH2:3]([O:5][C:6]1[CH:39]=[CH:38][CH:37]=[CH:36][C:7]=1[O:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:16]=[CH:17][C:18]([C:21]([NH:23][CH2:24][C:25]3[CH:26]=[C:27]([CH:32]=[C:33]([CH3:35])[CH:34]=3)[C:28]([OH:30])=[O:29])=[O:22])=[CH:19][N:20]=2)[CH2:10]1)[CH3:4]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 131737073Methyl (R)-3-((2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)methyl)-5-methylbenzoate

Product 1

HCID 118366180HCID 118366180, compoundYield 71.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Aqueous 1N sodium hydroxide solution (1.2 mL, 1.2 mmol) was added to a solution of methyl (R)-3-((2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)methyl)-5-methylbenzoate (123 mg, 0.24 mmol) in THF (5 mL). The reaction mixture was heated to 60° C. for 48 hours, and then the volatiles were evaporated under reduced pressure. The remaining aqueous phase was washed with diethyl ether (10 mL). The aqueous phase was then adjusted to pH 3 with aqueous 1N HCl (1 mL), and then was extracted with EtOAc (2 times with 10 mL). The combined organic phases were washed with brine (2 times with 10 mL), dried over MgSO4, filtered, and concentrated to provide (R)-3-((2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)methyl)-5-methylbenzoic acid (84.4 mg, 60%). 1H NMR (500 MHz, CDCl3) δ 8.77 (br s, 2H), 7.84 (s, 1H), 7.81 (s, 1H), 7.41 (s, 1H), 7.00 (d, 1H), 6.95 (m, 1H), 6.87 (m, 2H), 6.48 (br s, 1H), 4.65 (d, 2H), 4.42 (m, 1H), 4.27 (m, 1H), 4.13 (m, 1H), 4.00 (m, 2H), 3.85 (m, 1H), 3.71 (m, 1H), 2.40 (s, 3H), 2.11 (m, 1H), 1.97 (m, 2H), 1.60 (m, 1H), 1.38 (t, 3H). MS (ES+) 491.1 (M+H).

Workup

  1. customthe volatiles were evaporated under reduced pressure
  2. washThe remaining aqueous phase was washed with diethyl ether (10 mL)
  3. extractionwas extracted with EtOAc (2 times with 10 mL)
  4. washThe combined organic phases were washed with brine (2 times with 10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-4e26ea9e388e4560898dc9c235fd35fd
Source dataset
uspto-grants-2016_09
Patent number
US09440949B2

Reaction notes

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