1,4-Dioxane → HCID 71186380, compound

HRID 712919Notes

Reaction equation

HRID 712919 reaction equation
[CH3:1][C:2]1([CH3:34])[CH2:6][N:5]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[C@@H:4]([C:18]([NH:20][C:21]2([C:24]3[CH:33]=[CH:32][C:27]([C:28]([O:30]C)=[O:29])=[CH:26][CH:25]=3)[CH2:23][CH2:22]2)=[O:19])[CH2:3]1.O1CCOCC1.O[Li].O>O>[CH3:1][C:2]1([CH3:34])[CH2:6][N:5]([CH2:7][C:8]2[CH:9]=[CH:10][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:12][CH:13]=2)[C@@H:4]([C:18]([NH:20][C:21]2([C:24]3[CH:25]=[CH:26][C:27]([C:28]([OH:30])=[O:29])=[CH:32][CH:33]=3)[CH2:22][CH2:23]2)=[O:19])[CH2:3]1

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 168937Lithium hydroxide, monohydrate2×HCID 71204730HCID 71204730, compound

Product 1

HCID 71186380HCID 71186380, compoundYield 36.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

(R)-methyl 4-(1-(4,4-dimethyl-1-(4-(trifluoromethyl)benzyl)pyrrolidine-2-carboxamido)cyclopropyl)benzoate (D151) (100 mg, 0.21 mmol) was partitioned between dioxane (2 ml) and water (2 ml) prior addition of LiOH H2O (35 mg, 0.84 mmol) and the resulting mixture was stirred at RT for 18 hrs. Dioxane was evaporated off and the aqueous solution acidified with acetic acid to pH˜4-5. A white solid precipitated which was filtered, dried under vacuum, then re-dissolved in dioxane (2 ml) and water (2 ml) and hydrolysed for additional 5 hrs after addition of LiOH H2O (18 mg, 0.42 mmol). Dioxane was evaporated off and the aqueous solution acidified with acetic acid to pH˜4-5. A white solid precipitated which was filtered and dried under vacuum, to afford the title compound (E34) (35.5 mg).

Workup

  1. customDioxane was evaporated off
  2. customA white solid precipitated which
  3. filtrationwas filtered
  4. customdried under vacuum
  5. dissolutionre-dissolved in dioxane (2 ml)
  6. customDioxane was evaporated off
  7. customA white solid precipitated which
  8. filtrationwas filtered
  9. customdried under vacuum

Sources & evidence

ORD record
ord-4fe5d63693114bfab4cd7e7f2aa34a4d
Source dataset
uspto-grants-2015_11
Patent number
US09181279B2

Reaction notes

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