p-Toluenesulfonic acid monohydrate → (R)-(-)-2,2-Dimethyl-3-(1-methylethylidene)cyclobutanecarboxylic acid

HRID 558011Notes

Reaction equation

HRID 558011 reaction equation
[CH3:1][C:2]1([CH3:12])[C@H:7]2[CH2:8][C@H:5]([C:6]2([CH3:10])[CH3:9])[C:4](=[O:11])[O:3]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[CH3:9][C:6]1([CH3:10])[C:7](=[C:2]([CH3:1])[CH3:12])[CH2:8][C@H:5]1[C:4]([OH:11])=[O:3]

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 11252234(1R,5S)-(+)-4,4,6,6-Tetramethyl-3-oxabicyclo[3.1.1]heptan-2-one

Product 1

HCID 11240713(R)-(-)-2,2-Dimethyl-3-(1-methylethylidene)cyclobutanecarboxylic acidYield 78.1%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A solution of 3.68 g (21.9 mmol) of 4a in 60 mL of benzene with 416 mg (2.19 mmol) of p-toluenesulfonic acid monohydrate was heated in an oil bath at 100-110° C. for 24 h. A mini Dean-Stark trap was used for azeotropic distillation. Benzene was evaporated on a rotary evaporator, and the residue was treated with 2N aqueous Na2CO3 solution. The basic aqueous solution was washed with ether, then acidified to pH 2 with hydrochloric acid, and again extracted with ether. The combined ether extracts were washed with water, brine, dried, and concentrated to give 2.87 g (17.1 mmol, 78% yield) of 5a as clear oil after chromatography (silica gel, eluted with 20% to 25% of ethyl acetate in hexanes). Optical purity: 79% ee (after methylation); [α]24D−22.0 (c 0.1, MeOH); 1H NMR (CDCl3): δ 1.19 (3H, s), 1.37 (3H, s), 1.48 (3H, s), 1.58 (3H, s), 2.55 (1H, m), 2.81 (2H, m); 13C NMR (C6D6): δ 183.49, 135.57, 123.27, 47.47, 45.09, 28.15, 25.94, 22.09, 19.51, 18.52; EI-MS m/z (%): 168 [M]+ (38), 153 (38), 135 (8), 125 (21), 123 (27), 107 (59), 93 (29), 81 (100), 67 (30), 53 (16), 41 (25); HREIMS: obsd. 168.1152, calcd. for C10H16O2 (M+): 168.1150.

Workup

  1. distillationA mini Dean-Stark trap was used for azeotropic distillation
  2. customBenzene was evaporated on a rotary evaporator
  3. additionthe residue was treated with 2N aqueous Na2CO3 solution
  4. washThe basic aqueous solution was washed with ether
  5. extractionagain extracted with ether
  6. washThe combined ether extracts were washed with water, brine
  7. customdried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-30235a338a004004bf5b47ad0d4b13a1
Source dataset
uspto-grants-2011_11
Patent number
US08062651B1

Reaction notes

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