Dichloromethane → 3-Fluoro-4-[4-(1-hydroxy-ethyl)-pyridin-3-yl]-benzonitrile

HRID 1897594Notes

Reaction equation

HRID 1897594 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1B1OC(C)(C)C(C)(C)O1)[C:5]#[N:6].Br[C:20]1[CH:21]=[N:22][CH:23]=[CH:24][C:25]=1[CH:26]([OH:28])[CH3:27].C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[C:20]1[CH:21]=[N:22][CH:23]=[CH:24][C:25]=1[CH:26]([OH:28])[CH3:27])[C:5]#[N:6]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 447552103-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 667978531-(3-Bromopyridin-4-yl)ethanol

Product 1

HCID 699382473-Fluoro-4-[4-(1-hydroxy-ethyl)-pyridin-3-yl]-benzonitrileYield 11.7%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To the solution of 3-Fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzonitrile (306 mg, 1.24 mmol), 1-(3-Bromo-pyridin-4-yl)-ethanol (250 mg, 1.24 mmol) and PdCl2(dppf). CH2Cl2 adduct (81 mg, 0.10 mmol) in DMF (6 mL) was added 2M Na2CO3 solution (1.55 ml, 3.09 mmol) under Nitrogen atmosphere. The mixture was stirred and heated at 100° C. for 4 hrs. After letting cool to room temperature, solvent was removed in vacuo. The resulting residue was dissolved in DCM and saturated NH4Cl solution. After extraction with DCM and separation, the combined extracts were concentrated and purified by ISCO 12 g (10% MeOH/DCM=0-25%) to give 3-Fluoro-4-[4-(1-hydroxy-ethyl)-pyridin-3-yl]-benzonitrile (35 mg, 11%) as colorless solid; ESI-MS m/z: 243 [M+1]+, Retention time 1.19 min. 1H-NMR (MeOD, 400 MHz) δ 1.26 (d, J=6.8 Hz, 3H), 4.71 (q, J=6.8 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 7.71 (dd, J=8.0, 1.6 Hz, 1H), 7.74 (d, J=9.6 Hz, 1H), 7.75 (d, J=5.2 Hz, 1H), 8.33 (s, 1H), 8.62 (d, J=5.2 Hz, 1H).

Workup

  1. temperatureAfter letting cool to room temperature
  2. customsolvent was removed in vacuo
  3. dissolutionThe resulting residue was dissolved in DCM
  4. extractionAfter extraction
  5. customwith DCM and separation
  6. concentrationthe combined extracts were concentrated
  7. custompurified by ISCO 12 g (10% MeOH/DCM=0-25%)

Sources & evidence

ORD record
ord-57d832c07f8e4e658bc368a01c6cc42d
Source dataset
uspto-grants-2013_08
Patent number
US08519134B2

Reaction notes

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