HCID 10923011, compound → HCID 51394198, compound

HRID 873503Notes

Reaction equation

HRID 873503 reaction equation
[C:1]1([C@:7]2([C:16]([O:18]C)=[O:17])[CH2:9][C@@H:8]2[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC([O-])(C)C.[K+]>CS(C)=O>[C:1]1([C@:7]2([C:16]([OH:18])=[O:17])[CH2:9][C@@H:8]2[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 10923011HCID 10923011, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 51394198HCID 51394198, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a round-bottom flask at room temperature was added (1S,2R)-methyl 1,2-diphenylcyclopropanecarboxylate (11.5 mmol, 2.91 g, 1.0 equiv.) in dry DMSO (24 mL). t-BuOK (25.4 mmol, 2.85 g, 2.2 equiv.) was added in several portions over 30 minutes under argon. The reaction was monitored by TLC technique until the starting material was consumed completely. The reaction mixture was cooled with ice bath and acidified by careful addition of saturated ammonium chloride (10 mL), followed by a slow addition of 1 N HCl aqueous (35 mL) with vigorous stirring until the pH value reached 3-4. Light yellow solid precipitate was collected by filtration, washed with water (3×5 mL), dissolved in ethyl acetate (100 mL), washed with brine (3×5 mL), dried over MgSO4, and concentrated in vacuo. The crude material was purified using flash column chromatography eluting with a 10:1 mixture of hexanes/ethyl acetate to provide the desired product as a white solid (1.64 g, 60% yield, >99% ee). 1H NMR (400 MHz, CDCl3) δ 7.15-7.14 (m, 3H), 7.08-7.03 (m, 5H), 7.06-6.79 (m, 2H), 3.18 (dd, J=9.4, 7.4 Hz, 1H), 2.21 (dd, J=9.4, 4.9 Hz, 1H), 1.97 (dd, J=7.4, 4.9 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 179.8, 136.1, 134.2, 132.1, 128.3, 127.99, 127.97, 127.5, 126.7, 37.4, 34.1, 20.9; HPLC (to improve the separation, the product was converted to the corresponding methyl ester prepared using dimethylsulfate/KOH in tetrahydrofuran under reflux), (S,S-Whelk, 1.5% isopropanol in hexane, 0.7 mL/min, 1 mg/mL, 30 min, UV 254 nm) retention times of 12.5 min (major) and 15.5 min (minor), >99% ee.

Workup

  1. customwas consumed completely
  2. temperatureThe reaction mixture was cooled with ice bath
  3. additionacidified by careful addition of saturated ammonium chloride (10 mL)
  4. additionfollowed by a slow addition of 1 N HCl aqueous (35 mL)
  5. filtrationLight yellow solid precipitate was collected by filtration
  6. washwashed with water (3×5 mL)
  7. dissolutiondissolved in ethyl acetate (100 mL)
  8. washwashed with brine (3×5 mL)
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customThe crude material was purified
  12. washeluting with a 10:1 mixture of hexanes/ethyl acetate

Sources & evidence

ORD record
ord-32405b5b28b9402394c26f00e62d2b6b
Source dataset
uspto-grants-2015_03
Patent number
US08975428B2

Reaction notes

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