2-Methyl-2-butene → 3-(2-Carboxy-phenoxy)-3-trifluoromethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1479052Notes

Reaction equation

HRID 1479052 reaction equation
Cl([O-])=O.[Na+].P([O-])(O)(O)=[O:6].[Na+].CC(=CC)C.[C:16]([O:20][C:21]([N:23]1[CH2:27][CH2:26][C:25]([O:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=2[CH:39]=[O:40])([C:28]([F:31])([F:30])[F:29])[CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17]>O.O1CCOCC1>[C:16]([O:20][C:21]([N:23]1[CH2:27][CH2:26][C:25]([O:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=2[C:39]([OH:6])=[O:40])([C:28]([F:29])([F:30])[F:31])[CH2:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

7

Reactant 4

HCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 896500783-(2-Formyl-phenoxy)-3-trifluoromethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 896499643-(2-Carboxy-phenoxy)-3-trifluoromethyl-pyrrolidine-1-carboxylic acid tert-butyl esterYield 102.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of sodium chlorite (120 mg; 1.32 mmol; 5 eq.) and sodium dihydrogenphosphate (127 mg; 1.06 mmol; 4 eq.) in water (2 mL) was added dropwise to a mixture of 2-methyl-2-butene (0.25 mL) and 3-(2-formyl-phenoxy)-3-trifluoromethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (95 mg; 0.26 mmol; 1 eq.) in 1,4-dioxane (2 mL). The reaction mixture was stirred at room temperature for 3 hours and the 1,4-dioxane concentrated in vacuo. The aqueous solution was diluted with water and the pH made acidic with 0.1M HCl. The mixture was extracted with EA (2×) and the combined organic phase was dried over magnesium sulfate and concentrated in vacuo to afford the title compound (100 mg, quantitative) as a colourless oil. HPLC (max plot) 93.5%, Rt 4.22 min. UPLC/MS: (MS−) 374.3 ([M−H]−).

Workup

  1. concentrationthe 1,4-dioxane concentrated in vacuo
  2. additionThe aqueous solution was diluted with water
  3. extractionThe mixture was extracted with EA (2×)
  4. dry with materialthe combined organic phase was dried over magnesium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f2bbedfd09744175981ac8c0f78060c6
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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