Water → 3-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(2-propen-1-yl)benzonitrile

HRID 1875098Notes

Reaction equation

HRID 1875098 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([F:20])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17](Br)[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.[CH2:21]([Sn](CCCC)(CCCC)CC=C)[CH2:22][CH2:23]C.C(OCC)(=O)C.O>CN(C)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>[NH2:1][CH2:2][C:3]1[C:4]([F:20])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([CH2:23][CH:22]=[CH2:21])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 90628AllyltributylstannaneHCID 68485937HCID 68485937, compound

Product 1

HCID 684835313-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(2-propen-1-yl)benzonitrileYield 68.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-bromobenzonitrile (0.62 g, 1.744 mmol), tributyl(2-propen-1-yl)stannane (0.924 g, 2.79 mmol) and Pd(PPh3)4 (0.201 g, 0.174 mmol) in N,N-Dimethylformamide (DMF) (14 ml) was heated in a microwave reactor at 120° C. for 30 min. The vessel was cooled to RT and ethyl acetate (200 mL) and water (200 mL) were added. The organic layer was separated, washed with brine (200 mL), dried over MgSO4, filtered and concentrated. The crude material was purified on silica gel (hexanes/ethyl acetate) to give 0.38 g of a mixture of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(2-propen-1-yl)benzonitrile and Bu3SnBr. The material was used without further purification. N4011-30-100. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.20-7.29 (m, 2H), 7.17 (s, 1H), 7.02 (s, 1H), 6.84 (s, 1H), 5.78-5.96 (m, 1H), 5.01-5.18 (m, 2H), 3.91 (s, 2H), 3.37 (d, 2H).

Workup

  1. temperatureThe vessel was cooled to RT
  2. customThe organic layer was separated
  3. washwashed with brine (200 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified on silica gel (hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-55a21c2cdb7942708b1b1fa4ad8c750f
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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