Isobutyl chloride → HCID 69311330, compound

HRID 2375947Notes

Reaction equation

HRID 2375947 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].[CH2:14]([Mg]Cl)[CH:15]([CH3:17])[CH3:16].C(Cl)C(C)C.[Mg]>C1COCC1>[OH:5][C@H:4]([C:12]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C@@H:6]([OH:13])[CH2:14][CH:15]([CH3:17])[CH3:16])[CH:1]([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 10554Isobutyl chlorideHCID 5462224MagnesiumHCID 12859260HCID 12859260, compoundHCID 178418368HCID 178418368, compound

Product 1

HCID 69311330HCID 69311330, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (3S)-3-isopropyl-1,3-dihydro-isobenzofuran-1-ol (14.11 g, 0.129 mol) in THF (250 ml) was added at reflux temperature through a Teflon tube, which ended under the surface in the reaction mixture, a solution of isobutyl magnesium chloride (freshly prepared from 0.387 mol isobutyl chloride and 0.58 mol magnesium in 250 ml of THF) slowly within 20 minutes under efficient stirring. The mixture was then quenched with a solution of ammonium chloride (10%). The organic layer was separated, and the solvent was removed on the rotavapor. The residue was re-dissolved in ethyl acetate (200 ml), and this solution was washed with water (150 ml) and brine (150 ml). After drying and removal of the solvent the product was obtained as a yellow oil (31.5 g). 1H/13C-NMR (300 MHz, CDCl3, HSQC/HMBC) δ/δ 0.78 (d, J=6.9 Hz)/19.00, 1.04 (d, J=6.5 Hz)/20.22 (2 i-Pr CH3); 0.95 (d, J=6.5 Hz)/23.87, 0.96 (d, J=6.5 Hz)/22.32 (2 i-Bu CH3); 1.80 (m)/25.33 (i-Bu CHMe2); 2.02 (m)/35.13 ((i-Pr CHMe2); 1.47/1.72 (m)/48.03 (CH2); 3.09 (br s, 2 OH); 4.53 (d, J=8.1 Hz)/77.55 (CH(OH)i-Pr); 5.08 (dd, J=4.7 Hz, J=9.5 Hz)/68.87 (CH(OH)i-Bu); 7.40 (m)/126.44 (Ar i-Bu ortho-CH); 7.21 (m)/127.37 (Ar meta-CH); 7.28 (m)/127.55 (Ar i-Pr ortho-CH); 7.23 (m)/127.71 (Ar meta-CH); 140.56 (Ar i-Pr ipso-C); 142.66 (Ar i-Bu ipso-CH).

Workup

  1. temperatureat reflux temperature through a Teflon tube
  2. customThe mixture was then quenched with a solution of ammonium chloride (10%)
  3. customThe organic layer was separated
  4. customthe solvent was removed on the rotavapor
  5. dissolutionThe residue was re-dissolved in ethyl acetate (200 ml)
  6. washthis solution was washed with water (150 ml) and brine (150 ml)
  7. customAfter drying
  8. customremoval of the solvent the product

Sources & evidence

ORD record
ord-77ed8e5aadc443d2b6ecf7ae41887d0d
Source dataset
uspto-grants-2008_12
Patent number
US07465838B2

Reaction notes

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