Potassium tert-butoxide → HCID 71076489, compound

HRID 873507Notes

Reaction equation

HRID 873507 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C@:11]1([C:26]([O:28]C)=[O:27])[CH2:13][C:12]1([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CC([O-])(C)C.[K+]>CS(C)=O>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C@:11]1([C:26]([OH:28])=[O:27])[CH2:13][C:12]1([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 86720728HCID 86720728, compound

Product 1

HCID 71076489HCID 71076489, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a round-bottom flask at room temperature was added (R)-methyl 1-(naphthalen-2-yl)-2,2-diphenylcyclopropanecarboxylate (18.5 mmol, 7.0 g, 1.0 equiv) in dry DMSO (50 mL). t−BuOK (41.0 mmol, 4.6 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 saturated ammonium chloride aqueous (15 mL), followed by a slow addition of 1 N HCl (40 mL) with vigorous stirring until the pH value reached 3-4. Sticky solid precipitate was collected by filtration, washed with water (3×5 mL), dissolved in ethyl acetate (150 mL), washed with brine (3×10 mL), dried over anhydrous MgSO4, and concentrated in vacuo. The crude material was purified using flash column chromatography eluting with a 4:1 mixture of hexanes/ethyl acetate to provide the desired product as a white solid (4.1 g, 61% yield. mp: 195-196° C.; [α]20D −361.7° (c=1.0, CHCl3); 1H NMR (400 MHz; CDCl3) δ 7.80-7.76 (m, 3H), 7.65-7.59 (m, 3H), 7.53-7.46 (m, 3H), 7.42-7.34 (m, 3H), 7.11-7.09 (m, 2H), 7.0-6.9 (m, 3H), 2.73 (d, J=5.2 Hz, 1H), 2.65 (d, J=5.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 177.4, 141.5, 139.1, 133.1, 132.7, 132.3, 130.3, 130.1, 129.8, 128.6, 128.4, 127.7, 127.6, 127.5, 126.9, 126.7, 126.2, 125.8, 125.7, 42.7, 23.4; IR (neat): 3058, 1687, 1448, 1300; HRMS (APCI) calcd for C26H21O2 (M+H)+ 365.15361. found 365.15349; HPLC (to improve the separation, the product was converted to the corresponding methyl ester prepared using dimethylsulfate/KOH in tetrahydrofuran under reflux), HPLC (ODH, 0.5% isopropanol in hexane, 1.0 mL/min, 1 mg/mL, 30 min, UV 254 nm) retention times of 8.6 min (major) and 9.6 min (minor), >99% ee.

Workup

  1. customwas consumed completely
  2. temperatureThe reaction mixture was cooled with ice bath
  3. additionfollowed by a slow addition of 1 N HCl (40 mL)
  4. filtrationSticky solid precipitate was collected by filtration
  5. washwashed with water (3×5 mL)
  6. dissolutiondissolved in ethyl acetate (150 mL)
  7. washwashed with brine (3×10 mL)
  8. dry with materialdried over anhydrous MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe crude material was purified
  11. washeluting with a 4:1 mixture of hexanes/ethyl acetate

Sources & evidence

ORD record
ord-8055514608324ba9b3629f618de8ee51
Source dataset
uspto-grants-2015_03
Patent number
US08975428B2

Reaction notes

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