Bromoform → 2-(Cyclopropylmethoxy)-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)acetic acid

HRID 512664Notes

Reaction equation

HRID 512664 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:14]=[CH:13][C:10]([CH:11]=O)=[CH:9][CH:8]=2)=[N:4][N:3]=1.[OH-:15].[K+].C(Br)(Br)Br.[OH-].[K+].[CH:23]1([CH2:26][OH:27])[CH2:25][CH2:24]1.C1([CH2:31][OH:32])CC1>O1CCOCC1>[CH:23]1([CH2:26][O:27][CH:11]([C:10]2[CH:13]=[CH:14][C:7]([C:5]3[O:6][C:2]([CH3:1])=[N:3][N:4]=3)=[CH:8][CH:9]=2)[C:31]([OH:32])=[O:15])[CH2:25][CH2:24]1

Participants

7

Reactant 5

HCID 5558BromoformHCID 14797Potassium HydroxideHCID 75644Cyclopropanemethanol2×HCID 106552074-(5-Methyl-1,3,4-oxadiazol-2-yl)benzaldehydeHCID 86657504KOH cyclopropylmethanol

Product 1

HCID 584320792-(Cyclopropylmethoxy)-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)acetic acid

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 4-(5-methyl-1,3,4-oxadiazol-2-yl)benzaldehyde (5.3 g, 27.7 mmol) in cyclopropylmethanol (25 mL) and anhydrous dioxane (25 mL) at 0° C. (bath temperature) was added several drops of a solution of KOH (7.77 g, 138.5 mmol) in cyclopropylmethanol (35 mL). Bromoform (3.1 mL, 35.2 mmol) was added, then the remaining KOH/cyclopropylmethanol solution was added over a period of 20 min. After stirring for 30 min, the reaction mixture was allowed to warm slowly to room temperature overnight then concentrated to dryness. After dissolving in a minimum amount of H2O, the residue was acidified to pH 1 with concentrated HCl. The aqueous mixture was extracted with EtOAc several times with the addition of brine to the aqueous layer during extraction. The combined organics were washed with brine, dried over Na2SO4 and concentrated in vacuo to give 2-(cyclopropylmethoxy)-2-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)acetic acid as a semisolid which was then recyrstallized from Et2O (0.5 g, 7% yield).

Workup

  1. concentrationthen concentrated to dryness
  2. dissolutionAfter dissolving in a minimum amount of H2O
  3. extractionThe aqueous mixture was extracted with EtOAc several times with the addition of brine to the aqueous layer during extraction
  4. washThe combined organics were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a251c49eeebd49ba9ba351c7d7c2933f
Source dataset
uspto-grants-2015_08
Patent number
US09102643B2

Reaction notes

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