2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 67427351, compound

HRID 1510291Notes

Reaction equation

HRID 1510291 reaction equation
Cl.[NH:2]1[CH2:6][CH2:5][C@H:4]([O:7][C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]3[N:18]=[C:19]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[O:20][C:21]=3[C:22]([F:25])([F:24])[F:23])=[O:16])=[CH:10][CH:9]=2)[CH2:3]1.[C:32]([O:36][C:37](=[O:45])[C:38]1[CH:43]=[CH:42][C:41](Br)=[CH:40][CH:39]=1)([CH3:35])([CH3:34])[CH3:33].CC(C)([O-])C.[Na+].C(C1C=C(C(C)C)C=C(C(C)C)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1)(C)C>O1CCOCC1>[C:32]([O:36][C:37](=[O:45])[C:38]1[CH:43]=[CH:42][C:41]([N:2]2[CH2:6][CH2:5][C@H:4]([O:7][C:8]3[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]4[N:18]=[C:19]([C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=5)[O:20][C:21]=4[C:22]([F:25])([F:23])[F:24])=[O:16])=[CH:10][CH:9]=3)[CH2:3]2)=[CH:40][CH:39]=1)([CH3:35])([CH3:33])[CH3:34]

Participants

6

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 11334366Tert-butyl 4-bromobenzoateHCID 23676156Sodium t-butoxideHCID 67440878HCID 67440878, compound

Product 1

HCID 67427351HCID 67427351, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

To a mixture of 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [4-((S)-pyrrolidin-3-yloxy)-phenyl]-amide hydrochloride (180 mg, 0.37 mmol), 4-bromobenzoic acid tert-butyl ester (114 mg, 0.44 mmol), sodium tert-butoxide (118 mg, 1.23 mmol) and (2′,4′,6′-triisopropyl-1,1′-biphenyl-2-yl)dicyclohexylphosphine (X-PHOS, 40 mg) in dioxane (5 mL) bubbled with argon was added tris(dibenzylideneacetone)dipalladium Pd2(dba)3 (24 mg). The mixture was heated at 105° C. for 2 hrs. Solvents were evaporated and the residue was extracted with ethyl acetate and 0.1N hydrochloric acid. The organic layer was dried and concentrated. The residue was purified through ISCO column chromatography (silica gel, ethyl acetate in hexane, 5% to 60% linear gradient) to give a white solid as 4-((S)-3-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenoxy}-pyrrolidin-1-yl)-benzoic acid tert-butyl ester (150 mg, yield 69%).

Workup

  1. custombubbled with argon
  2. additionwas added tris(dibenzylideneacetone)dipalladium Pd2(dba)3 (24 mg)
  3. customSolvents were evaporated
  4. extractionthe residue was extracted with ethyl acetate and 0.1N hydrochloric acid
  5. customThe organic layer was dried
  6. concentrationconcentrated
  7. customThe residue was purified through ISCO column chromatography (silica gel, ethyl acetate in hexane, 5% to 60% linear gradient)

Sources & evidence

ORD record
ord-89493e155283444cb82b6e12d50c8ef0
Source dataset
uspto-grants-2012_07
Patent number
US08211914B2

Reaction notes

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