Dichloromethane → HCID 86674840, compound

HRID 1897602Notes

Reaction equation

HRID 1897602 reaction equation
[F:1][CH:2]([F:21])[O:3][C:4]1[CH:11]=[C:10](B2OC(C)(C)C(C)(C)O2)[CH:9]=[CH:8][C:5]=1[C:6]#[N:7].Br[C:23]1[CH:24]=[N:25][CH:26]=[CH:27][C:28]=1[CH:29]([OH:31])[CH3:30].C(Cl)[Cl:33].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]>[Cl:33][C:23]1[C:28]([CH:29]([OH:31])[CH3:30])=[C:27]([C:10]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:3][CH:2]([F:1])[F:21])[CH:11]=2)[CH:26]=[N:25][CH:24]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 667978531-(3-Bromopyridin-4-yl)ethanolHCID 69938119HCID 69938119, compound

Product 1

HCID 86674840HCID 86674840, compoundYield 288.1%

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 2-difluoromethoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzonitrile (927 mg, 3.14 mmol), 1-(3-Bromo-pyridin-4-yl)-ethanol (634 mg, 3.14 mmol) and PdCl2(dppf). CH2Cl2 adduct (256 mg, 0.31 mmol) in DMF (12 mL) was added a solution of Na2CO3 (2M, 3.14 ml, 6.28 mmol) under Nitrogen atmosphere. The mixture was stirred and heated at 100° C. for 6 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 the residue was purified by ISCO 40 g (EtOAc/Heptane, v/v, 0-90%) to give 4-[5-Chloro-4-(1-hydroxy-ethyl)-pyridin-3-yl]-2-difluoromethoxy-benzonitrile (290 mg, 32%) as a white solid; ESI-MS m/z: 291 [M+1]+, Retention time 1.28 min; 1H-NMR (CDCl3, 400 MHz) δ 1.41 (d, J=6.8 Hz, 3H), 4.92 (q, J=6.8 Hz, 1H), 6.72 (t, J=71.2 Hz, 1H), 7.31 (dd, J=8.0, 1.2 Hz, 1H), 7.36 (d, J=1.2 Hz, 1H), 7.70 (d, J=5.2 Hz, 1H), 7.79 (d, J=8.0 Hz, 1H), 8.44 (s, 1H), 8.71 (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. customthe residue was purified by ISCO 40 g (EtOAc/Heptane, v/v, 0-90%)

Sources & evidence

ORD record
ord-b374fc788d73476dba649e9ba4cf5eb0
Source dataset
uspto-grants-2013_08
Patent number
US08519134B2

Reaction notes

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