Hydrogen Peroxide → (S)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)-2-(2-fluoro-4-(trifluoromethyl)phenyl)acetic acid

HRID 2279550Notes

Reaction equation

HRID 2279550 reaction equation
[OH:1][Li].O.OO.C([C@@H]1COC(=O)N1C(=O)[C@H:20]([C@H:32]1[N:36]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C:35]([CH3:45])([CH3:44])[CH2:34][CH2:33]1)[C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][C:22]=1[F:31])C1C=CC=CC=1.[O-]S([O-])=O.[Na+].[Na+].C1[CH2:57][O:56]CC1.O>C1COCC1>[C:40]([O:39][C:37]([N:36]1[C:35]([CH3:44])([CH3:45])[CH2:34][CH2:33][C@H:32]1[C@H:20]([C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:28])([F:30])[F:29])=[CH:23][C:22]=1[F:31])[C:57]([OH:56])=[O:1])=[O:38])([CH3:43])([CH3:41])[CH3:42]

Participants

7

Reactant 5

HCID 784Hydrogen PeroxideHCID 24437Sodium SulfiteHCID 168937Lithium hydroxide, monohydrateHCID 21881883Oxolane--water (1/1)HCID 86705538(S)-tert-butyl 5-((S)-2-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-(2-fluoro-4-(trifluoromethyl)phenyl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate

Product 1

HCID 86705537(S)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)-2-(2-fluoro-4-(trifluoromethyl)phenyl)acetic acidYield 83.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of LiOH—H2O (0.3177 g, 7.570 mmol) in THF/water (2:1, 240 mL) was added 30% H2O2(0.91 mL, 9.46 mmol) and the soln stirred at RT for 10 min. The solution was cooled to 0° C. and a solution of 320 (2.19 g, 3.785 mmol) in THF (10 mL) was added. The reaction was stirred at 0° C. for 2 h then warmed to RT and stirred overnight. The reaction was then cooled to 0° C. and treated with 1M Na2SO3 (10 mL) and stirred for 10 min then warmed to RT and stirred for 10 min. The reaction was concentrated and extracted with EtOAc (2×20 mL). The aqueous phase was acidified with H2SO4 to pH ca. I-2 and extracted with DCM (2×20 mL). The organic extracts were concentrated and the crude product purified C18 preparative MPLC (Analogix 200 g C18 column) to afford 1.321 g (83.2%) of (S)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)-2-(2-fluoro-4-(trifluoromethyl)phenyl)acetic acid (322).

Workup

  1. temperatureThe solution was cooled to 0° C.
  2. stirringThe reaction was stirred at 0° C. for 2 h
  3. temperaturethen warmed to RT
  4. stirringstirred overnight
  5. temperatureThe reaction was then cooled to 0° C.
  6. stirringstirred for 10 min
  7. temperaturethen warmed to RT
  8. stirringstirred for 10 min
  9. concentrationThe reaction was concentrated
  10. extractionextracted with EtOAc (2×20 mL)
  11. extractionextracted with DCM (2×20 mL)
  12. concentrationThe organic extracts were concentrated
  13. customthe crude product purified C18 preparative MPLC (Analogix 200 g C18 column)

Sources & evidence

ORD record
ord-4859f813e20e4505859995bd6d19a308
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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