Hydrochloric Acid → (1S,5R)-1-(1-naphthyl)-3-oxabicyclo[3.1.0]hexan-2-one

HRID 1096751Notes

Reaction equation

HRID 1096751 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:5][C@:4]1([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=1)[C:6]#N.[OH-:18].[Na+].Cl>ClCCl>[C:8]1([C@:4]23[CH2:5][C@H:3]2[CH2:2][O:1][C:6]3=[O:18])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66781614(1S)-2-Hydroxymethyl-1-(1-naphthyl)-cyclopropanecarbonitrile

Product 1

HCID 66781232(1S,5R)-1-(1-naphthyl)-3-oxabicyclo[3.1.0]hexan-2-oneYield 44%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(1S)-2-hydroxymethyl-1-(1-naphthyl)-cyclopropanecarbonitrile (300 mg, 1.3 mmol) ethanol (0.6 mL) and 25N sodium hydroxide solution (0.3 mL) were heated under reflux for 18 hours. The reaction is monitored by TLC (dichloromethane (100%)). The reaction mixture was cooled to room temperature and ice cold water (12 mL) was added to the reaction mixture followed by concentrated hydrochloric acid drop to adjust the pH of the reaction mass to 1-2 and stirred for overnight. The aqueous layer was extracted with dichloromethane (25 mL). The organic layer was washed with 3% sodium bicarbonate solution, dried over anhydrous sodium sulphate, filtered and evaporated under reduced pressure to yield 128 mg (44%) of product. 1H NMR δ(300 MHz,CDCl3): 1.51-1.54 (1H,t, J=4.58,), 1.74-1.78 (1H,dd, J=7.7,4.8 Hz), 2.53-2.57 (1H,m), 4.43-4.46 (1H,d,J=9.5 Hz), 4.71-4.76 (1H,dd,J=9.3,4.5 Hz), 7.40-7.58 (4H,m), 7.83-7.89 (2H,m), 7.95-7.98 (1H d,J=8.2 Hz).

Workup

  1. temperatureunder reflux for 18 hours
  2. extractionThe aqueous layer was extracted with dichloromethane (25 mL)
  3. washThe organic layer was washed with 3% sodium bicarbonate solution
  4. dry with materialdried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-6cb500454c5f4f3d857b912c797e566d
Source dataset
uspto-grants-2012_03
Patent number
US08138377B2

Reaction notes

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