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

HRID 1096761Notes

Reaction equation

HRID 1096761 reaction equation
C1(S(C2(SC)[CH2:15][C@@H:14]3[C@@:12]([C:16]4[C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[CH:19]=[CH:18][CH:17]=4)([CH2:13]3)[CH2:11]2)(=O)=O)C=CC=CC=1.[CH3:28][OH:29].Cl>C(OCC)(=O)C.CCCCCC>[C:16]1([C@@:12]23[CH2:13][C@@H:14]2[CH2:15][C:28](=[O:29])[CH2:11]3)[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 86622517(1R,5R)-3-Benzenesulfonyl-1-(1-naphthyl)-3-methylsulfanyl-bicyclo[3.1.0]hexane

Product 1

HCID 66781762(1R,5R)-1-(1-naphthyl)bicyclo[3.1.0]hexan-3-oneYield 99%

Reagents, catalysts & solvents 1

HCID 21226206Ethyl acetate hexaneSolvent

Procedure

(1R,5R)-3-Benzenesulfonyl-1-(1-naphthyl)-3-methylsulfanyl-bicyclo[3.1.0]hexane (620 mg, 1.6 mmol), methanol (4 mL) and concentrated hydrochloric acid (0.7 mL) were heated to reflux for 7 hours. The reaction was monitored by TLC (ethyl acetate/hexane (20:80)) The reaction mixture was concentrated under reduced pressure to remove methanol. The pH of the reaction mass was adjusted to 8-9 with saturated sodium bicarbonate solution. The aqueous layer was extracted with diethyl ether (50 mL). The organic layer was washed with water, dried over anhydrous sodium sulphate, filtered and evaporated under reduced pressure to yield 458 mg of crude oil, which was purified by preparative HPLC to yield 135 mg (39%) of 99% pure product. 1H NMR δ(300 MHz,CDCl3) 0.76-0.79 (1H,t, J=4 Hz), 1.38 (1H,m), 2.01 (1H,m), 2.49-2.56 (1H,d, J=10Hz), 2.75 (2H,d,J=6 Hz), 3.05-3.15 (2H,dd,J=10 Hz), 7.40-7.45 (1H,m), 7.50-7.56 (3H,m), 7.76-7.79 (1H,d,J=9 Hz), 7.88-7.90 (1H,m), 8.13-8.15 (2H,d ,J=6 Hz). 13CNMR(CDCl3)δ: 218.25, 139.12, 134.01, 128.96, 127.80, 126.77, 126.17, 125.78, 125.33, 124.0, 48.18, 42.46, 27.80, 20.62, 20.05.

Workup

  1. temperatureto reflux for 7 hours
  2. concentrationwas concentrated under reduced pressure
  3. customto remove methanol
  4. extractionThe aqueous layer was extracted with diethyl ether (50 mL)
  5. washThe organic layer was washed with water
  6. dry with materialdried over anhydrous sodium sulphate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customto yield 458 mg of crude oil, which
  10. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-4a7d370c90ef4b9cb9db4d34c7581dbc
Source dataset
uspto-grants-2012_03
Patent number
US08138377B2

Reaction notes

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