Sodium Hydroxide → HCID 59382342, compound

HRID 1809805Notes

Reaction equation

HRID 1809805 reaction equation
C(OC([N:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:13]=[C:14]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:15]=[CH:16][CH:17]=2)[C@@H:8]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][C:27]=2[O:33][CH2:34][CH2:35][CH2:36][O:37][CH3:38])[CH2:7]1)=O)C.[OH-].[Na+]>C(O)C>[C:14]1([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:15]=[CH:16][CH:17]=[C:12]([C@H:9]2[CH2:10][CH2:11][NH:6][CH2:7][C@@H:8]2[O:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][C:27]=2[O:33][CH2:34][CH2:35][CH2:36][O:37][CH3:38])[CH:13]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 67542367HCID 67542367, compound

Product 1

HCID 59382342HCID 59382342, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
170 °C

Procedure

To a solution of the title D compound, (3R,4R)-4-biphenyl-3-yl-3-[2-(3-methoxy-propoxy)-4-methyl-benzyloxy]-piperidine-1-carboxylic acid ethyl ester (50 mg, 0.95 mmol) in 2 mL of absolute ethanol is added 2 mL of a 10% aqueous solution of sodium hydroxide. The resulting mixture is heated at 170° C. for 45 min in a microwave. The solvent is removed under reduced pressure and the resulting aqueous suspension is extracted twice with methylene chloride. The combined organic layers are dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue is purified by preparative HPLC (Macherey-Nagel 250/4 nucleosil 100-10 C18 column, 20:80 CH3CN+0.1% TFA over 11 min, then 100% CH3CN+0.1% TFA for 5.5 min, 40 mL/min). To the combined fractions containing the desired product is added 1M aqueous sodium carbonate solution and the acetonitrile is removed under reduced pressure. The resulting aqueous suspension is extracted twice with ethyl acetate. The combined organic layers are dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure affording the title compound as a colorless oil. A solution of the compound in acetonitrile is lyophilized. MS 446.1 [M+H]. Rt (HPLC, Nucleosil C18, 10:90-100:0 CH3CN/H2O+0.1% TFA within 5 min, then 100% CH3CN+0.1% TFA): 5.48 min.

Workup

  1. customThe solvent is removed under reduced pressure
  2. extractionthe resulting aqueous suspension is extracted twice with methylene chloride
  3. dry with materialThe combined organic layers are dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by preparative HPLC (Macherey-Nagel 250/4 nucleosil 100-10 C18 column, 20:80 CH3CN+0.1% TFA over 11 min
  7. additionTo the combined fractions containing the desired product
  8. additionis added 1M aqueous sodium carbonate solution
  9. customthe acetonitrile is removed under reduced pressure
  10. extractionThe resulting aqueous suspension is extracted twice with ethyl acetate
  11. dry with materialThe combined organic layers are dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-06ee17f213a3418bb9e805d1dd8489fe
Source dataset
uspto-grants-2013_01
Patent number
US08362040B2

Reaction notes

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