Dichloromethane → (1S,2S,4S)-4-(2',4'-Difluoro-3-trifluoromethyl-biphenyl-4-sulfonyl)-2-methoxy-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amide

HRID 1367483Notes

Reaction equation

HRID 1367483 reaction equation
[C:1]([C:3]1([NH:6][C:7]([C@H:9]2[CH2:13][C@H:12]([S:14]([C:17]3[CH:22]=[CH:21][C:20](Br)=[CH:19][C:18]=3[C:24]([F:27])([F:26])[F:25])(=[O:16])=[O:15])[CH2:11][C@@H:10]2[O:28][CH3:29])=[O:8])[CH2:5][CH2:4]1)#[N:2].[F:30][C:31]1[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl.C([O-])(O)=O.[Na+]>CN(C=O)C.O>[C:1]([C:3]1([NH:6][C:7]([C@H:9]2[CH2:13][C@H:12]([S:14]([C:17]3[CH:22]=[CH:21][C:20]([C:34]4[CH:33]=[CH:32][C:31]([F:30])=[CH:36][C:35]=4[F:37])=[CH:19][C:18]=3[C:24]([F:27])([F:26])[F:25])(=[O:16])=[O:15])[CH2:11][C@@H:10]2[O:28][CH3:29])=[O:8])[CH2:5][CH2:4]1)#[N:2]

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 27343342,4-Difluorophenylboronic acidHCID 59619475(1S,2S,4S)-4-(4-Bromo-2-trifluoromethyl-benzenesulfonyl)-2-methoxy-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amide

Product 1

HCID 59619336(1S,2S,4S)-4-(2',4'-Difluoro-3-trifluoromethyl-biphenyl-4-sulfonyl)-2-methoxy-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amideYield 84.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Argon was bubbled through a mixture of (1R,2R,4R) and (1S,2S,4S)-4-(4-bromo-2-trifluoromethyl-benzenesulfonyl)-2-methoxy-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amide (30 mg, 0.0606 mmol, example 58), 2.4-difluorophenylboronic acid (11 mg, 0.0727 mmol) and Na2CO3 (17 mg, 0.1635 mmol) in DMF (1.5 ml) and water (81.8 ul) for 15 min. Then [1,1′-bis(diphenyl-phosphino)ferrocene]palladium(II) chloride 1:1 complex with DCM (5 mg, 0.00606 mmol) was added and the orange mixture was heated to 80° C. for 3 h. The mixture was then cooled to room temperature, poured onto a mixture of saturated NaHCO3 solution and ice and extracted 3 times with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and evaporated. The remaining brown solid was purified by silica gel chromatography (DCM/MeOH 98:2) to obtain the title compound (27 mg, 84%) as off-white solid. MS (EI): 529.2 (M+H)+.

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. extractionextracted 3 times with EtOAc
  3. washThe combined extracts were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe remaining brown solid was purified by silica gel chromatography (DCM/MeOH 98:2)

Sources & evidence

ORD record
ord-c1ec22e6c66b405a9a13bb311f397df6
Source dataset
uspto-grants-2011_02
Patent number
US07893099B2

Reaction notes

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