Imidazole → HCID 67457927, compound

HRID 625065Notes

Reaction equation

HRID 625065 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[C:9]([C:15]#[N:16])[C:10]([O:12]CC)=O)=[CH:4][CH:3]=1.[BH4-].[Na+].[Si:19](Cl)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].ClC1C=CC(CC(CO)C#N)=CC=1.N1C=CN=C1>CC(O)C.CN(C=O)C>[Si:19]([O:12][CH2:10][CH:9]([CH2:8][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)[C:15]#[N:16])([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]

Participants

8

Reactant 5

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 367499HCID 367499, compoundHCID 4311764Sodium borohydrideHCID 14669438HCID 14669438, compound

Product 1

HCID 67457927HCID 67457927, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolvent2×HCID 6228DimethylformamideSolvent2×

Procedure

A solution of ethyl 3-(4-chlorophenyl)-2-cyanoacrylate (6.2 g, 26 mmol) in 2-propanol (80 mL) was added dropwise to a stirred suspension of NaBH4 (2.8 g, 74 mmol) in 2-propanol (20 mL). The mixture was stirred at room temperature overnight. Excess NaBH4 was destroyed with saturated NH4Cl, and most of the 2-propanol was removed in vacuo. The residue was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried and concentrated. The crude 2-(4-chlorobenzyl)-3-hydroxypropanenitrile was used without purification. TBS-Cl (2.77 g, 18.4 mmol) in dry DMF (15 mL) was added to a solution of the crude 2-(4-chlorobenzyl)-3-hydroxypropanenitrile (3.00 g, 15.3 mmol) and imidazole (4.18 g, 61.3 mmol) in DMF (25 mL) at 0° C. under nitrogen. The reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was partitioned between ether and water. The organic layer was washed with brine, dried and concentrated. The residue was purified by column (hexanes:EtOAc, 30:1) to give 3-(tert-butyldimethylsilyloxy)-2-(4-chlorobenzyl)propanenitrile (3.70 g, 78%) as a colorless oil.

Workup

  1. customExcess NaBH4 was destroyed with saturated NH4Cl
  2. custommost of the 2-propanol was removed in vacuo
  3. customThe residue was partitioned between EtOAc and water
  4. extractionThe aqueous layer was extracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. customdried
  7. concentrationconcentrated
  8. customThe crude 2-(4-chlorobenzyl)-3-hydroxypropanenitrile was used without purification
  9. temperatureThe reaction mixture was warmed to room temperature
  10. stirringstirred overnight
  11. customThe reaction mixture was partitioned between ether and water
  12. washThe organic layer was washed with brine
  13. customdried
  14. concentrationconcentrated
  15. customThe residue was purified by column (hexanes:EtOAc, 30:1)

Sources & evidence

ORD record
ord-6c20aa6e8dc147ba82cb5d89f8e0ecbe
Source dataset
uspto-grants-2016_04
Patent number
US09303040B2

Reaction notes

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