Diethyl Carbonate → HCID 58573918, compound

HRID 1048294Notes

Reaction equation

HRID 1048294 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[C:11](=[O:26])[C@:10]([CH2:28][C@H:29]([OH:33])[C:30]([NH2:32])=[O:31])([CH3:27])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[O-:34][CH2:35]C.[Na+].C(=O)(OCC)OCC>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH:21]([CH2:22][CH3:23])[CH2:24][CH3:25])[C:11](=[O:26])[C@:10]([CH2:28][CH:29]3[O:33][C:35](=[O:34])[NH:32][C:30]3=[O:31])([CH3:27])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 7766Diethyl CarbonateHCID 2723922Sodium ethoxideHCID 58573942HCID 58573942, compound

Product 1

HCID 58573918HCID 58573918, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 10.3 mg (0.02 mmol) of (S)-3-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)-2-hydroxypropanamide (Example 81, Step D) in MeOH (2.5 mL) was added 0.50 mL (1.22 mmol) of sodium ethoxide (21 wt. % solution in ethanol) and 1.20 mL (9.90 mmol) of diethyl carbonate. The resulting mixture was heated at reflux for 15 min, and then was concentrated under reduced pressure. The residue was partitioned between 0.5 M HCl and EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by reversed phase prep. HPLC (Sunfire™ Prep C18 OBD 10 μm column (Waters, Milford, Mass.), gradient elution of 60 MeCN in water to 80 MeCN in water over a 30 min period, where both solvents contain 0.1% TFA) provided the title compound (mixture of ether epimers) as a white solid.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 15 min
  3. concentrationwas concentrated under reduced pressure
  4. customThe residue was partitioned between 0.5 M HCl and EtOAc (3×)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. customPurification of the residue by reversed phase prep
  9. washHPLC (Sunfire™ Prep C18 OBD 10 μm column (Waters, Milford, Mass.), gradient elution of 60 MeCN in water to 80 MeCN in water over a 30 min period, where both solvents

Sources & evidence

ORD record
ord-2acac38f643c422f8b5acaf3a0179bde
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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