Phosphorus oxychloride → (1R,5S)-(+)-4,4,6,6-Tetramethyl-3-oxabicyclo[3.1.1]heptan-2-one

HRID 558010Notes

Reaction equation

HRID 558010 reaction equation
O[C:2]([C@H:5]1[CH2:8][C@@H:7]([C:9]([OH:11])=[O:10])[C:6]1([CH3:13])[CH3:12])([CH3:4])[CH3:3].P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[CH3:3][C:2]1([CH3:4])[C@H:5]2[CH2:8][C@H:7]([C:6]2([CH3:13])[CH3:12])[C:9](=[O:11])[O:10]1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 11480888(1R,3S)-3-(1-hydroxy-1-methylethyl)-2,2-dimethylcyclobutanecarboxylic acid

Product 1

HCID 11252234(1R,5S)-(+)-4,4,6,6-Tetramethyl-3-oxabicyclo[3.1.1]heptan-2-oneYield 75%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 2.66 g (14.28 mmol) of alcohol 3a in 15 mL of pyridine was added dropwise in 1.40 mL (15.00 mmol) of phosphorus oxychloride at ice-water cooling. The mixture was stirred at room temperature for 24 h, poured onto 75 g of ice, and extracted with ether. The ether extracts were washed with water, 2N hydrochloric acid, then water, saturated aqueous solution of sodium hydrogen carbonate, and brine. After drying over sodium sulfate, the solvent was removed, and the residue was purified by chromatography (30/70, ethyl acetate/hexanes) to afford 1.8 g (10.71 mmol) of pure lactone 4a in 75% yield. Optical purity: 80% ee; [α]24D+5.0 (c 0.1, MeOH); 1H NMR (CDCl3): δ 1.14 (3H, s), 1.37 (3H, s), 1.38 (3H, s), 1.49 (3H, s), 1.81 (1H, d, J=10.59 Hz), 2.10 (1H, dd, J=6.05, 5.67 Hz), 2.48 (1H, ddd, J=10.59, 5.67, 5.30 Hz), 2.63 (1H, dd, J=6.05, 5.30 Hz); 13C NMR (CDCl3): δ 175.04, 82.44, 50.34, 50.01, 40.91, 29.11, 26.11, 25.81, 25.27, 25.25; EI-MS m/z (%): 153 (26), 125 (20), 110 (40), 109 (55), 95 (100), 83 (27), 69 (72), 68 (78), 67 (60), 55 (42), 43 (35), 41 (38); HREIMS: obsd. 153.0911, calcd. for C9H13O2 (M+—CH3): 153.0916.

Workup

  1. extractionextracted with ether
  2. washThe ether extracts were washed with water, 2N hydrochloric acid
  3. dry with materialAfter drying over sodium sulfate
  4. customthe solvent was removed
  5. customthe residue was purified by chromatography (30/70, ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-91578635e56a4eafa881ec3041e53417
Source dataset
uspto-grants-2011_11
Patent number
US08062651B1

Reaction notes

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