Beta-Propiolactone → 3-[3',5'-Dichloro-4'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-yloxy]-propionic acid

HRID 2235297Notes

Reaction equation

HRID 2235297 reaction equation
[CH:1]1([N:7]2[CH2:11][CH2:10][CH:9]([CH2:12][C:13]3[C:18]([Cl:19])=[CH:17][C:16]([C:20]4[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=4)=[CH:15][C:14]=3[Cl:27])[C:8]2=[O:28])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[C:35]1(=[O:39])[O:38][CH2:37][CH2:36]1>C1COCC1>[Cl:19][C:18]1[CH:17]=[C:16]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:37][CH2:36][C:35]([OH:39])=[O:38])=[CH:22][CH:21]=2)[CH:15]=[C:14]([Cl:27])[C:13]=1[CH2:12][CH:9]1[CH2:10][CH2:11][N:7]([CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[C:8]1=[O:28]

Participants

5

Reactant 3

HCID 2365Beta-PropiolactoneHCID 23665647Potassium tert-butoxideHCID 592993351-Cyclohexyl-3-(3,5-dichloro-4'-hydroxy-biphenyl-4-ylmethyl)-pyrrolidin-2-one

Product 1

HCID 592994563-[3',5'-Dichloro-4'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-yloxy]-propionic acidYield 11.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Treat a solution of 1-cyclohexyl-3-(3,5-dichloro-4′-hydroxy-biphenyl-4-ylmethyl)-pyrrolidin-2-one (55) (0.20 g, 0.47 mmol) in THF (3 mL) with a 1 molar solution of potassium tert-butoxide in THF (0.50 mL, 0.49 mmol) and stir for 5 minutes at room temperature. Add dropwise a solution of beta-propiolactone (0.038 g, 0.527 mmol) in THF (3 mL) and stir the reaction at room temperature for 16 hours under N2. Quench the reaction with 1 N HCl, extract with ethyl acetate and water, dry the organic layer (Na2SO4) and purify by normal phase chromatography (30 to 100% gradient of ethyl acetate in hexanes) to afford 26 mg (11%) of the title compound: LC-MS (ES+) m/z=exact mass calcd for C26H29Cl2NO4 489, found 490 and 492 (M+1 and M+3, 100%).

Workup

  1. stirringstir
  2. customthe reaction at room temperature for 16 hours under N2
  3. customQuench
  4. customthe reaction with 1 N HCl
  5. extractionextract with ethyl acetate and water
  6. dry with materialdry the organic layer (Na2SO4)
  7. custompurify by normal phase chromatography (30 to 100% gradient of ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-18474537e293437faee4886f0ce4b6ee
Source dataset
uspto-grants-2010_05
Patent number
US07713979B2

Reaction notes

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