Dichloromethane → HCID 69267558, compound

HRID 750790Notes

Reaction equation

HRID 750790 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@@H:8]1[CH2:13][CH2:12][C:11]([F:15])([F:14])[CH2:10][C@H:9]1[C:16]([NH:18][C:19]1([C:22]#[N:23])[CH2:21][CH2:20]1)=[O:17].[CH3:24][S:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>CN(C)C=O.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:22]([C:19]1([NH:18][C:16]([C@@H:9]2[CH2:10][C:11]([F:15])([F:14])[CH2:12][CH2:13][C@H:8]2[C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[C:29]2[CH:30]=[CH:31][C:26]([S:25][CH3:24])=[CH:27][CH:28]=2)=[O:17])[CH2:21][CH2:20]1)#[N:23]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27339594-(Methylthio)phenylboronic acidHCID 69268929HCID 69268929, compound

Product 1

HCID 69267558HCID 69267558, compound

Reagents, catalysts & solvents 2

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

Procedure

(1R,2R)-2-(2-Bromophenyl)-N-(1-cyanocyclopropyl)-5,5-difluorocyclohexanecarboxamide (518 mg, 1.35 mmol), 4-(methylthio) benzeneboronic acid (285 mg, 1.70 mmol), PdCl2(dppf).CH2Cl2 (61 mg, 0.075 mmol) and 2.0 M Na2CO3 aqueous solution (1.02 mL, 2.04 mmol) were heated at 85° C. in N,N-dimethylformamide (4.0 mL) under a nitrogen atmosphere. After 17 hours at this temperature, the reaction mixture was cooled to room temperature and partitioned between ethyl acetate and water and the layers separated. The aqueous phase was extracted with additional ethyl acetate and the combined organics were washed with brine, and dried (Na2SO4). Concentration in vacuo and chromatography of the residue on silica eluting with 30/70 EtOAc/hexanes gave the title compound as a faint-yellow foam, [αD=−41° (c=0.95, CHCl3), MS (−ESI): 425.3 [M−H]−.

Workup

  1. custompartitioned between ethyl acetate and water
  2. customthe layers separated
  3. extractionThe aqueous phase was extracted with additional ethyl acetate
  4. washthe combined organics were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationConcentration in vacuo and chromatography of the residue on silica eluting with 30/70 EtOAc/hexanes

Sources & evidence

ORD record
ord-8b6a87fdbef94b96824308b2dd706e5d
Source dataset
uspto-grants-2008_07
Patent number
US07405229B2

Reaction notes

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