N-methyl-2-pyrrolidone → 2-Tert-butoxy-2-(1-(4-chlorophenyl)-4-cyano-3-methylnaphthalen-2-yl)acetic acid

HRID 514149Notes

Reaction equation

HRID 514149 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[C:4]([CH:19]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[C:20]([O:22]C)=[O:21])[C:3]=1[CH3:29].[C:30]([Cu])#[N:31].CN1C(=O)CCC1>CCO>[C:25]([O:24][CH:19]([C:4]1[C:3]([CH3:29])=[C:2]([C:30]#[N:31])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]=1[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1)[C:20]([OH:22])=[O:21])([CH3:26])([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 67126267Methyl 2-(4-bromo-1-(4-chlorophenyl)-3-methylnaphthalen-2-yl)-2-tert-butoxyacetateHCID 178418546HCID 178418546, compound

Product 1

HCID 671263162-Tert-butoxy-2-(1-(4-chlorophenyl)-4-cyano-3-methylnaphthalen-2-yl)acetic acidYield 57.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
200 °C

Procedure

A suspension of methyl 2-(4-bromo-1-(4-chlorophenyl)-3-methylnaphthalen-2-yl)-2-tert-butoxyacetate (10.5 mg, 22.1 μmol), CuCN (9.8 mg, 0.11 mmol), and NMP (500 μL) was heated to 200° C. in a microwave. The reaction was cooled to 23° C., treated with EtOH (2.5 mL), filtered through a 0.45 micron filter, and directly purified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA). The product-containing fractions were combined and treated with LiOH monohydrate until the pH was distinctly basic. The mixture was concentrated with warming to remove most of the water and all of the CH3CN. The solution was treated with EtOH (absolute, 500 μL) and THF (1.0 mL). The suspension was stirred at 23° C. for 1 h. It was filtered through a 0.45 micron filter, and directly purified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA). The product-containing fractions were combined and lyophilized, giving the title compound (parent form) (5.2 mg, 55% over 2 steps).

Workup

  1. temperatureThe reaction was cooled to 23° C.
  2. filtrationfiltered through a 0.45 micron
  3. filtrationfilter
  4. customdirectly purified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA)
  5. additiontreated with LiOH monohydrate until the pH
  6. concentrationThe mixture was concentrated
  7. temperaturewith warming
  8. customto remove most of the water
  9. additionThe solution was treated with EtOH (absolute, 500 μL) and THF (1.0 mL)
  10. filtrationIt was filtered through a 0.45 micron
  11. filtrationfilter
  12. customdirectly purified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-bde06fe26a96414bb8fbc1ed9ed9f99c
Source dataset
uspto-grants-2015_08
Patent number
US09102614B2

Reaction notes

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