Dichloromethane → HCID 70654855, compound

HRID 879128Notes

Reaction equation

HRID 879128 reaction equation
[F:1][C:2]1[CH:7]=[C:6](OS(C(F)(F)F)(=O)=O)[CH:5]=[C:4]([F:16])[C:3]=1[C:17]1[N:22]=[C:21]([C:23]([O:25][CH3:26])=[O:24])[CH:20]=[CH:19][C:18]=1[F:27].[S:28]1[CH2:33][CH:32]=[C:31](B(O)O)[CH2:30][CH2:29]1.C(Cl)Cl>COCCOC.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]>[S:28]1[CH2:29][CH:30]=[C:31]([C:6]2[CH:5]=[C:4]([F:16])[C:3]([C:17]3[N:22]=[C:21]([C:23]([O:25][CH3:26])=[O:24])[CH:20]=[CH:19][C:18]=3[F:27])=[C:2]([F:1])[CH:7]=2)[CH2:32][CH2:33]1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 70655370HCID 70655370, compoundHCID 86670164HCID 86670164, compound

Product 1

HCID 70654855HCID 70654855, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a degassed solution of methyl 6-(2,6-difluoro-4-(trifluoromethylsulfonyloxy)phenyl)-5-fluoropicolinate (1.0 equiv.) and 3,6-dihydro-2H-thiopyran-4-ylboronic acid (1.5 equiv.) in DME/2M Na2CO3 (3/1, 0.10 M) was added PdCl2(dppf).CH2Cl2 adduct (0.10 equiv.). The reaction was heated to 90° C. in an oil bath for 15 min. The reaction mixture was partitioned with water and EtOAc; the organics were dried over MgSO4, filtered, and concentrated. The crude was purified via ISCO SiO2 chromatography. Pure fractions were combined and concentrated to yield methyl 6-(4-(3,6-dihydro-2H-thiopyran-4-yl)-2,6-difluorophenyl)-5-fluoropicolinate in 60% yield. LC/MS=366.1 (M+H), Rt=1.00 min.

Workup

  1. customThe reaction mixture was partitioned with water and EtOAc
  2. dry with materialthe organics were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude was purified via ISCO SiO2 chromatography
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-98e701c6e4ce41009510f254e1911a03
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Reaction notes

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