Isobutyraldehyde → HCID 59189502, compound

HRID 333479Notes

Reaction equation

HRID 333479 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[C:5]#[N:6].C(=O)=O.C(O)(C)C.C1([Mg]Br)C=CC=CC=1.[CH:28](=[O:32])[CH:29]([CH3:31])[CH3:30]>O1CCCC1>[C:5]([C:4]1[CH:7]=[CH:8][C:9]([N+:10]([O-:12])=[O:11])=[C:2]([CH:28]([OH:32])[CH:29]([CH3:31])[CH3:30])[CH:3]=1)#[N:6]

Participants

6

Reactant 4

HCID 6561IsobutyraldehydeHCID 12125938Benzonitrile, 3-iodo-4-nitro-HCID 86586944Isopropanol carbon dioxideHCID 178418255HCID 178418255, compound

Product 1

HCID 59189502HCID 59189502, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-iodo-4-nitrobenzonitrile (314 mg, 1.14 mmol) in anhydrous tetrahydrofuran (5.5 mL) cooled at minus 45° C. (dry ice-isopropanol bath) under nitrogen atmosphere, phenylmagnesium bromide (2 M in THF, 3.16 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 (0.957 mL, 10.54 mmol) was added. The mixture was allowed to gradually warm up to room temperature, then quenched with saturated NH4Cl (2 mL) and poured into water (50 mL)/dichloromethane (50 mL). The organic layer was separated; aqueous layer was extracted three times with dichloromethane (25 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-(5-cyano-2-nitrophenyl)-2-methyl-1-propanol (57 mg, 23%) as a light yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.93 (d, 1H, J=8.1 Hz, Ph-H), 7.74 (s, 1H, Ph-H), 7.21 (d, 1H, J=8.1 Hz, Ph-H), 4.72 (d, 1H, J=3.6 Hz, Ph-CH), 2.33 (br. s, 1H, OH), 2.03 (m, 1H, CHCH(CH3)2), 1.04 (d, 3H, J=6.8 Hz, CH3), 0.89 (d, 3H, J=6.6 Hz, CH3); 13C NMR (100 MHz, CDCl3): δ 147.78 (C), 140.25 (CH), 131.40 (CH), 131.24 (CH), 118.36 (C), 112.27 (CN), 103.82 (C), 80.80 (CH), 33.56 (CH), 19.70 (CH3), 15.62 (CH3).

Workup

  1. custom40° C
  2. additionUpon completion of the addition the mixture
  3. customquenched with saturated NH4Cl (2 mL)
  4. additionpoured into water (50 mL)/dichloromethane (50 mL)
  5. customThe organic layer was separated
  6. extractionaqueous layer was extracted three times with dichloromethane (25 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-7f3a3509177d4913800b4b84255c9e91
Source dataset
uspto-grants-2014_11
Patent number
US08877905B2

Reaction notes

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