2-(Methyloxy)-4-(2-oxoethyl)benzonitrile → 4-(2-Hydroxypropyl)-2-methoxybenzonitrile

HRID 1186974Notes

Reaction equation

HRID 1186974 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[C:9]([CH2:11][CH:12]=[O:13])[CH:8]=[CH:7][C:4]=1[C:5]#[N:6].[CH3:14][Mg]Br>ClCCl.C1COCC1>[OH:13][CH:12]([CH3:14])[CH2:11][C:9]1[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[C:3]([O:2][CH3:1])[CH:10]=1

Participants

5

Reactant 2

HCID 772312592-(Methyloxy)-4-(2-oxoethyl)benzonitrileHCID 178418573HCID 178418573, compound

Product 1

HCID 666438784-(2-Hydroxypropyl)-2-methoxybenzonitrile

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-methoxy-4-(2-oxoethyl)benzonitrile (1.5 g, 8.5 mmol) in dichloromethane (30 mL) at 0° C. was added 2.8 mL (8.5 mmol) of a 3.0 M solution of methylmagnesium bromide in THF. The reaction mixture was allowed to warm up to rt and stirred for 12 h. The reaction was then quenched by the addition of 10 mL of 1 N hydrochloric acid and extracted with dichloromethane (2×30 mL). The combined organic extracts were dried with magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was purified on silica (30% EtOAc/hexanes as eluent) to afford 4-(2-hydroxypropyl)-2-methoxybenzonitrile. 1H NMR (500 MHz, CDCl3) δ 7.47 (d, 1H, J=7.8 Hz), 6.85 (dd, 1H, J=3.4 Hz), 6.82 (s, 1H), 4.05 (m, 1H), 3.93 (d, 2H), 3.91 (s, 3H), 1.25 (d, 2H, J=6.1 Hz); LCMS: [(M+1)]+=192.30; tR=2.39 min.

Workup

  1. customThe reaction was then quenched by the addition of 10 mL of 1 N hydrochloric acid
  2. extractionextracted with dichloromethane (2×30 mL)
  3. dry with materialThe combined organic extracts were dried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified on silica (30% EtOAc/hexanes as eluent)

Sources & evidence

ORD record
ord-14c49d41b80d4045a2ff4cc51323f93f
Source dataset
uspto-grants-2014_03
Patent number
US08673920B2

Reaction notes

Loading…