Ethanol → 5-(Diethoxymethyl)-2-fluorobenzonitrile

HRID 1467659Notes

Reaction equation

HRID 1467659 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:7](C=O)=[CH:6][C:3]=1[C:4]#[N:5].C(O)C.[CH:15]([O:22][CH2:23][CH3:24])([O:19][CH2:20][CH3:21])OCC>[Cl-].[NH4+]>[CH2:23]([O:22][CH:15]([O:19][CH2:20][CH3:21])[C:7]1[CH:8]=[CH:9][C:2]([F:1])=[C:3]([CH:6]=1)[C:4]#[N:5])[CH3:24]

Participants

5

Reactant 3

HCID 702EthanolHCID 31214Ethyl orthoformateHCID 27695822-Fluoro-5-formylbenzonitrile

Product 1

HCID 547587945-(Diethoxymethyl)-2-fluorobenzonitrileYield 98.5%

Reagents, catalysts & solvents 1

HCID 25517Ammonium ChlorideCatalyst

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 2-fluoro-5-formylbenzonitrile (5.96 g, 40 mmol) in ethanol (5.6 g, 120 mmol) was added ammonium chloride (85.6 mg, 1.6 mmol). After the addition, the mixture was cooled to 0° C. and triethyl orthoformate (6.52 g, 44 mmol) was added dropwise. After the addition, the mixture was stirred at room temperature overnight. The mixture was concentrated, then filtered and the cake washed with ethyl acetate (20 mL×2). The filtrate was concentrate to give the title compound (8.8 g, yield 98%) as a colorless oil. 1H-NMR (400 MHz, CDCl3) δ (ppm): 1.22-1.29 (m, 6H), 3.50-3.70 (m, 4H), 5.50 (s, 1H), 7.19-7.24 (t, J=8.8 Hz, 1H), 7.70-7.74 (m, 1H), 7.76-7.78 (dd, J1=6.4 Hz, J2=2.4 Hz, 1H). LC-MS (ESI) m/z: 224 (M+1)+

Workup

  1. additionAfter the addition
  2. additionAfter the addition
  3. concentrationThe mixture was concentrated
  4. filtrationfiltered
  5. washthe cake washed with ethyl acetate (20 mL×2)
  6. concentrationThe filtrate was concentrate

Sources & evidence

ORD record
ord-ef6ebd8fb9b8457ab6d171e9431ffde8
Source dataset
uspto-grants-2015_04
Patent number
US08999987B2

Reaction notes

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