Potassium Carbonate → 2-Isopropoxy-5-(thiophen-2-yl)benzonitrile

HRID 1891497Notes

Reaction equation

HRID 1891497 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:10][CH:11]([CH3:13])[CH3:12])=[C:6]([CH:9]=1)[C:7]#[N:8].[S:14]1[CH:18]=[CH:17][CH:16]=[C:15]1B(O)O.C(=O)([O-])[O-].[K+].[K+].CC(O)C(O)C.O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:11]([O:10][C:5]1[CH:4]=[CH:3][C:2]([C:15]2[S:14][CH:18]=[CH:17][CH:16]=2)=[CH:9][C:6]=1[C:7]#[N:8])([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 27339602-Thiopheneboronic acidHCID 32624945-Bromo-2-isopropoxybenzonitrileHCID 122674143dimethylethylene glycol H2O

Product 1

HCID 583672852-Isopropoxy-5-(thiophen-2-yl)benzonitrileYield 82%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A microwave vial was charged with 5-bromo-2-isopropoxybenzonitrile (200 mg, 0.83 mmol), thiophen-2-ylboronic acid (106.5 mg, 0.83 mmol), potassium carbonate (345.3 mg, 2.49 mmol) and 3:1 mixture of dimethylethylene glycol/H2O (2 mL). The reaction mixture was degassed by bubbling N2 gas through the stirred solution for 10 min. Pd(PPh3)4 (20.4 mg, 0.02 mmol) was added and the solution degassed for additional 2 min. The vial was subjected to microwave irradiation at 100° C. for 30 min. The solvent was removed and the residue dissolved in EA (10 mL), washed with brine, and dried over MgSO4. The product was purified chromatography (EA/hexanes) to afford 165 mg (82%) of 2-isopropoxy-5-(thiophen-2-yl)benzonitrile TRIO INT-1 as colorless oil. LCMS-ESI (m/z) calculated for C14H13NOS: 243.1; found 266.0 [M+Na]+, tR=3.90 min. 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J=2.3 Hz, 1H), 7.69 (dd, J=8.8, 2.4 Hz, 1H), 7.28-7.23 (m, 1H), 7.19 (dd, J=3.6, 1.1 Hz, 1H), 7.05 (dd, J=5.1, 3.6 Hz, 1H), 6.95 (d, J=8.8 Hz, 1H), 4.65 (dt, J=12.2, 6.1 Hz, 1H), 1.43-1.37 (m, 6H).

Workup

  1. customThe reaction mixture was degassed
  2. customby bubbling N2 gas through the stirred solution for 10 min
  3. customthe solution degassed for additional 2 min
  4. customirradiation at 100° C. for 30 min
  5. customThe solvent was removed
  6. dissolutionthe residue dissolved in EA (10 mL)
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. customThe product was purified chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-5538b08cf5d843058c7ed46768e27813
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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