1-Bromo-4-(dimethoxymethyl)benzene → HCID 58456703, compound

HRID 2036132Notes

Reaction equation

HRID 2036132 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([O:11][CH3:12])[O:9][CH3:10])=[CH:4][CH:3]=1.[Li][CH2:14][CH2:15][CH2:16][CH3:17].[O:18]1CC(=O)C1>O1CCCC1>[CH3:10][O:9][CH:8]([O:11][CH3:12])[C:5]1[CH:6]=[CH:7][C:2]([C:17]2([OH:18])[CH2:16][CH2:15][CH2:14]2)=[CH:3][CH:4]=1

Participants

5

Reactant 3

HCID 6883421-Bromo-4-(dimethoxymethyl)benzeneHCID 150242543-OxetanoneHCID 178418339Butyllithium

Product 1

HCID 58456703HCID 58456703, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cold (−78° C.) solution of 1-bromo-4-(dimethoxymethyl)benzene BB1a (693 mg, 3 mmol) in anhydrous tetrahydrofuran (10 mL) is added n-BuLi (2.5 M in hexanes, 1.32 mL, 3.3 mmol) and the mixture is stirred for 45 min under nitrogen atmosphere. Oxetan-3-one (216 mg, 3 mmol) in anhydrous tetrahydrofuran (2 mL) is added and the cooling bath is removed. The reaction mixture is stirred for 2 h, saturated NH4Cl (5 mL) is added and the mixture is stirred for another 15 min. Tetrahydrofuran is evaporated, water is added and the mixture is extracted with ethyl acetate (4×). The combined organic phase is dried (Na2SO4), filtered and concentrated. Purification by flash chromatography (hexanes/ethyl acetate gradient) affords 1-(4-(dimethoxymethyl)phenyl)cyclobutanol BB1b as white crystals: 1H-NMR (400 MHz, DMSO-d6) δ=7.60 (m, 2H), 7.40 (m, 2H), 6.37 (s, 1H), 5.39 (s, 1H), 4.76 (d, J=6.8 Hz, 2H), 4.67 (d, J=6.8 Hz, 2H), 3.24 (s, 6H).

Workup

  1. customthe cooling bath is removed
  2. stirringThe reaction mixture is stirred for 2 h
  3. additionsaturated NH4Cl (5 mL) is added
  4. stirringthe mixture is stirred for another 15 min
  5. customTetrahydrofuran is evaporated
  6. additionwater is added
  7. extractionthe mixture is extracted with ethyl acetate (4×)
  8. dry with materialThe combined organic phase is dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by flash chromatography (hexanes/ethyl acetate gradient)

Sources & evidence

ORD record
ord-6aa15241a1524dd58a2de26f227d4b4c
Source dataset
uspto-grants-2013_11
Patent number
US08575168B2

Reaction notes

Loading…