Hydrochloric Acid → 5-(4-Chlorophenyl)pyridin-2-amine

HRID 1625011Notes

Reaction equation

HRID 1625011 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][N:3]=1.[Cl:9][C:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1.C([O-])([O-])=O.[Na+].[Na+].Cl>O1CCOCC1.O.CC([O-])=O.CC([O-])=O.[Pd+2].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].C(Cl)Cl>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:13]2[CH:14]=[CH:15][C:10]([Cl:9])=[CH:11][CH:12]=2)=[CH:4][N:3]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 706222-Amino-5-bromopyridineHCID 742994-Chlorophenylboronic acid

Product 1

HCID 132426445-(4-Chlorophenyl)pyridin-2-amineYield 78%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6344DichloromethaneSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

2-Amino-5-bromopyridine (2) was reacted with 4-chlorophenylboronic acid (3) in dioxane/water in the presence of 2.2 equivalents of Na2CO3 and 1 mol % Pd(OAc)2 plus 1 mol % PdCl2(dppf).CH2Cl2 at 90° C. for 1.5 h. After cooling to room temperature the product (4) was precipitated as the HCl salt by adding HCl (25%, 6 equiv) followed by removal of dioxane under vacuum. The salt was filtered, digested in diethylether, filtered and then converted to the free amine by treatment with aqueous NaOH. After filtration, the product was isolated in 78% yield. Alternatively, the product has been isolated by chromatography in 83% yield. MS (Turbo Spray): 207 (52%), 205 (M+H+, 100%), 170 (9%).

Workup

  1. customwas precipitated as the HCl salt
  2. customfollowed by removal of dioxane under vacuum
  3. filtrationThe salt was filtered
  4. filtrationfiltered
  5. filtrationAfter filtration
  6. customthe product was isolated in 78% yield
  7. customAlternatively, the product has been isolated by chromatography in 83% yield

Sources & evidence

ORD record
ord-63c015e1fd1048578a2d27d061261e94
Source dataset
uspto-grants-2014_07
Patent number
US08779150B2

Reaction notes

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