Sulfuric Acid → Ethyl 1-(benzoylamino)-α-methylcyclobutaneacetate

HRID 444774Notes

Reaction equation

HRID 444774 reaction equation
OS(O)(=O)=O.O[C:7]1([CH:11]([CH3:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:10][CH2:9][CH2:8]1.[OH-:18].[Na+].[C:20](#[N:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>>[C:20]([NH:27][C:7]1([CH:11]([CH3:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:10][CH2:9][CH2:8]1)(=[O:18])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

5

Reactant 4

HCID 1118Sulfuric AcidHCID 7505BenzonitrileHCID 14798Sodium HydroxideHCID 58134867HCID 58134867, compound

Product 1

HCID 58134862Ethyl 1-(benzoylamino)-α-methylcyclobutaneacetateYield 46%

Procedure

H2SO4 (3.90 mL, 73.2 mmol) was slowly added to a mixture of ethyl 2-(1-hydroxycyclobutyl)propionate (12.5 g, 72.6 mmol) and benzonitrile (75 mL) at room temperature. The mixture was stirred for 1 hour at room temperature, then 80° C. for 1 hour. The mixture was cooled in an ice-water bath and 2N NaOH solution was added until the mixture reached pH=7. The mixture was extracted with ethyl acetate, the combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Flash chromatography (AcOEt:Hexane=5:1) of the residue gave the title compound as a pale yellow solid (9.24 g, 46%). 1H-NMR (400 MHz, CDCl3) δ 1.25 (3H, t, J=7.3 Hz), 1.30 (3H, d, J=7.3 Hz), 1.73-1.87 (1H, m), 1.98-2.09 (2H, m), 2.21-2.32 (1H, m), 2.53-2.63 (1H, m), 2.84-2.94 (1H, m), 3.11 (1H, q, J=7.3 Hz), 4.08-4.20 (2H, m), 6.88 (1H, brs), 7.40-7.52 (3H, m), 7.75-7.80 (2H, m).

Workup

  1. wait80° C. for 1 hour
  2. temperatureThe mixture was cooled in an ice-water bath
  3. extractionThe mixture was extracted with ethyl acetate
  4. dry with materialthe combined organic extracts were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dab986d497ff4b698bf46798112733e7
Source dataset
uspto-grants-2013_07
Patent number
US08476261B2

Reaction notes

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