HCID 12859260, compound → HCID 69311580, compound

HRID 2375946Notes

Reaction equation

HRID 2375946 reaction equation
[CH:1]([C@H:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]([OH:13])[O:5]1)([CH3:3])[CH3:2].[CH:14]([Mg]Cl)([CH3:16])[CH3:15]>C1COCC1.CCOCC>[OH:5][C@H:4]([C:12]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C@@H:6]([OH:13])[CH:14]([CH3:16])[CH3:15])[CH:1]([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 12859260HCID 12859260, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 69311580HCID 69311580, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (3S)-3-isopropyl-1,3-dihydro-isobenzofuran-1-ol (2.0 g, 11.2 mmol) in THF (20 mL) was heated under an atmosphere of nitrogen at reflux. To this solution was added slowly a solution of isopropyl magnesium chloride (39.3 mmol) in THF (ca. 20 ml). This solution had been prepared from the commercial solution (19.6 ml 2N solution in ether), from which the solvent had been removed in vacuum, and where the residue was made up with THF to a volume of 20 ml). After the addition of the Grignard reagent was completed, the mixture was stirred for another 30 minutes, and then allowed to cool to ambient temperature. To the mixture was then added a 10% solution of ammonium chloride (ca. 30 ml). The aqueous layer was removed, and re-extracted with TBME (ca. 20 ml). From the combined organic layers the solvent was removed, and the residue was redissolved in TBME (ca. 50 ml). After washing with water and brine, the organic layer was dried (Na2SO4). Removal of the solvent left the product as an oil, 2.2 g (88%). There was only one isomer present by 13C-NMR, which turned out to be the (S,S)-diol. 1H/13C-NMR (CDCl3, HSQC/HMBC) δ/δ 0.783 (d, J=6.7 Hz)/20.02 (CH3); 1.065 (d, J=6.5 Hz)/18.99 (CH3); 2.02 (m)/35.29 (CHMe2); 4.60 (d, J=7.6 Hz)/76.51 (CH(OH)); 2.38 br s (OH); 7.20-7.26 (m)/126.75 (Ar ortho-CH); 7.33-7.39 (m)/127.55 (Ar meta-CH); 141.41 (Ar ipso-C).

Workup

  1. temperatureat reflux
  2. customhad been removed in vacuum, and where the residue
  3. additionAfter the addition of the Grignard reagent
  4. additionTo the mixture was then added a 10% solution of ammonium chloride (ca. 30 ml)
  5. customThe aqueous layer was removed
  6. extractionre-extracted with TBME (ca. 20 ml)
  7. customFrom the combined organic layers the solvent was removed
  8. dissolutionthe residue was redissolved in TBME (ca. 50 ml)
  9. washAfter washing with water and brine
  10. dry with materialthe organic layer was dried (Na2SO4)
  11. customRemoval of the solvent
  12. waitleft the product as an oil, 2.2 g (88%)

Sources & evidence

ORD record
ord-6a227f5f15c34ac1a30d5022713be12c
Source dataset
uspto-grants-2008_12
Patent number
US07465838B2

Reaction notes

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