Diethyl Carbonate → HCID 58573918, compound

HRID 931982Notes

Reaction equation

HRID 931982 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-5416f9a2e05046279a67fbde15b96f67
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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