Dichloromethane → HCID 69937824, compound

HRID 1897604Notes

Reaction equation

HRID 1897604 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8](B2OC(C)(C)C(C)(C)O2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].Br[C:20]1[CH:21]=[N:22][CH:23]=[C:24]([F:31])[C:25]=1[C:26]1([OH:30])[CH2:29][O:28][CH2:27]1.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]>[Cl:1][C:2]1[CH:9]=[C:8]([C:20]2[CH:21]=[N:22][CH:23]=[C:24]([F:31])[C:25]=2[C:26]2([OH:30])[CH2:29][O:28][CH2:27]2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 579261132-Chloro-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 67155049HCID 67155049, compound

Product 1

HCID 69937824HCID 69937824, compoundYield 6.1%

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-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (409 mg, 1.55 mmol), 3-(3-Bromo-5-fluoro-pyridin-4-yl)-oxetan-3-ol (350 mg, 1.41 mmol) and PdCl2(dppf).CH2Cl2 adduct (115 mg, 0.141 mmol) in DMF (7 mL) was added a solution of Na2CO3 (2M in water, 1.76 ml, 3.53 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 (0-40%, v/v, EtOAc/Heptane) to give 2-Chloro-4-[5-fluoro-4-(3-hydroxy-oxetan-3-yl)-pyridin-3-yl]-benzonitrile (26 mg, 6%) as colorless solid; ESI-MS m/z: 305 [M++1]+, Retention time 1.27 min; 1H-NMR (CDCl3, 400 MHz) δ 4.42 (d, J=8.4 Hz, 2H), 4.66 (d, J=8.4 Hz, 2H), 7.57 (d, J=6.8 Hz, 1H), 7.76 (s, 1H), 7.80 (d, J=6.8 Hz, 1H), 8.41 (s, 1H), 8.59 (s, 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 (0-40%, v/v, EtOAc/Heptane)

Sources & evidence

ORD record
ord-830cffc46ea54f5c9b21056d8d10c40d
Source dataset
uspto-grants-2013_08
Patent number
US08519134B2

Reaction notes

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