Dimethylformamide → tert-Butyl 3-(3-cyanophenethoxy)propanoate

HRID 909899Notes

Reaction equation

HRID 909899 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][CH2:6][O:7][CH2:8][CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].[CH3:20][N:21](C=O)C>C(OCC)(=O)C.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.[C-]#N.[Zn+2].[C-]#N>[C:20]([C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][CH2:6][O:7][CH2:8][CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])#[N:21]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 67075913tert-Butyl 3-(3-bromophenethoxy)propanoate

Product 1

HCID 58168561tert-Butyl 3-(3-cyanophenethoxy)propanoate

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

Pd(Ph3P)4 (0.53 g) was added in one portion to tert-butyl 3-(3-bromophenethoxy)propanoate [Preparation 3, Step i)] (3.00 g), and zinc cyanide (1.68 g) in DMF (35 mL) under nitrogen. The resulting mixture was stirred at 130° C. for 30 min. The reaction mixture was diluted with ethyl acetate (100 mL) and filtered through Celite. Isohexane (100 mL) was added and the mixture was washed with water (4×20 mL). The organic layer was dried over magnesium sulfate, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0-20% ethyl acetate in isohexane to afford the subtitled compound (2.30 g). 1H NMR (300 MHz, CDCl3) δ 7.54-7.43 (m, 3H), 7.41-7.34 (m, 1H), 3.67 (t, J=6.3 Hz, 2H), 3.66 (t, J=6.6 Hz, 2H), 2.89 (t, J=6.5 Hz, 2H), 2.47 (t, J=6.3 Hz, 2H), 1.43 (s, 9H).

Workup

  1. filtrationfiltered through Celite
  2. additionIsohexane (100 mL) was added
  3. washthe mixture was washed with water (4×20 mL)
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customto afford crude product
  8. customThe crude product was purified by flash silica chromatography, elution gradient 0-20% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-56b794228eee4ba984bce8d8ee347465
Source dataset
uspto-grants-2011_09
Patent number
US08017602B2

Reaction notes

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