Isobutyraldehyde → (R/S)-1-(4-methoxy-2-nitrophenyl)-2-methyl-1-propanol

HRID 1499655Notes

Reaction equation

HRID 1499655 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5](OC)=[C:4]([N+:10]([O-:12])=[O:11])[CH:3]=1.[C:13](=O)=[O:14].C(O)(C)C.C1([Mg]Cl)C=CC=CC=1.[CH:28](=[O:32])[CH:29]([CH3:31])[CH3:30]>O1CCCC1>[CH3:13][O:14][C:2]1[CH:7]=[CH:6][C:5]([CH:28]([OH:32])[CH:29]([CH3:31])[CH3:30])=[C:4]([N+:10]([O-:12])=[O:11])[CH:3]=1

Participants

6

Reactant 4

HCID 6561IsobutyraldehydeHCID 122498664-Iodo-2-nitroanisoleHCID 86586944Isopropanol carbon dioxideHCID 178478979HCID 178478979, compound

Product 1

HCID 59189447(R/S)-1-(4-methoxy-2-nitrophenyl)-2-methyl-1-propanolYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-iodo-2-nitroanisole (2.79 g, 10.00 mmol) in anhydrous tetrahydrofuran (20 mL) cooled at minus 45° C. (dry ice-isopropanol bath) under nitrogen atmosphere, phenylmagnesium chloride (2 M in THF, 6 mL, 6.32 mmol) was added at a rate to keep the temperature at or below minus 40° C. Upon completion of the addition the mixture was stirred for five minutes, then isobutyraldehyde (1.816 mL, 20.00 mmol) was added. The mixture was allowed to gradually warm up to room temperature, then quenched with saturated NH4Cl (5 mL) and poured into water (30 mL)/dichloromethane (100 mL). The organic layer was separated; aqueous layer was extracted three times with dichloromethane (50 mL each). Combined organic extract was dried over anhydrous Na2SO4, concentrated under reduced pressure, and purified by silica gel column chromatography to yield racemic (RS)-1-(4-methoxy-2-nitrophenyl)-2-methyl-1-propanol (1.502 g, 30%) as a yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.62 (AB d, 1 H, J=8.8 Hz, Ph-H), 7.34 (d, 1 H, J=2.6 Hz, Ph-H), 7.15 (dd, 1 H, J=2.6 and 8.8 Hz, Ph-H), 4.91 (m, 1 H, Ph-CH), 3.86 (s, 3H, MeO), 2.45 (br s, 1 H, OH), 2.00 (m, 1 H, CHCH, (CH3)2), 0.97 (d, 3 H, J=6.7 Hz, CH3), 0.86 (d, 3 H, J=6.9 Hz, CH3); 13C NMR (100 MHz, CDCl3): δ 158.76 (C), 149.07 (C), 130.79 (C), 129.88 (CH), 119.62 (CH), 108.66 (CH), 73.75 (CH), 55.81 (CH3), 34.27 (CH), 19.59 (CH3), 17.36 (CH3).

Workup

  1. custom40° C
  2. additionUpon completion of the addition the mixture
  3. customquenched with saturated NH4Cl (5 mL)
  4. additionpoured into water (30 mL)/dichloromethane (100 mL)
  5. customThe organic layer was separated
  6. extractionaqueous layer was extracted three times with dichloromethane (50 mL each)
  7. extractionCombined organic extract
  8. dry with materialwas dried over anhydrous Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-44abd531d78b4574867f13429998a80a
Source dataset
uspto-grants-2015_12
Patent number
US09200319B2

Reaction notes

Loading…