2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 4-(4-{4-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidin-1-yl)-benzoic acid tert-butyl ester

HRID 1510293Notes

Reaction equation

HRID 1510293 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[N:17]=[C:18]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[O:19][C:20]=3[C:21]([F:24])([F:23])[F:22])=[O:15])=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.[C:31]([O:35][C:36](=[O:44])[C:37]1[CH:42]=[CH:41][C:40](Br)=[CH:39][CH:38]=1)([CH3:34])([CH3:33])[CH3:32].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:31]([O:35][C:36](=[O:44])[C:37]1[CH:42]=[CH:41][C:40]([N:1]2[CH2:6][CH2:5][CH:4]([C:7]3[CH:8]=[CH:9][C:10]([NH:13][C:14]([C:16]4[N:17]=[C:18]([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)[O:19][C:20]=4[C:21]([F:22])([F:23])[F:24])=[O:15])=[CH:11][CH:12]=3)[CH2:3][CH2:2]2)=[CH:39][CH:38]=1)([CH3:34])([CH3:32])[CH3:33]

Participants

6

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 11334366Tert-butyl 4-bromobenzoateHCID 23676156Sodium t-butoxideHCID 529371572-Phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (4-piperidin-4-yl-phenyl)-amide

Product 1

HCID 674271094-(4-{4-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidin-1-yl)-benzoic acid tert-butyl esterYield 12.3%

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-piperidin-4-yl-phenyl)-amide (227 mg, 0.55 mmol), 4-bromobenzoic acid tert-butyl ester (170 mg, 0.66 mmol), sodium tert-butoxide (106 mg, 1.1 mmol) and (2′,4′,6′-triisopropyl-1,1′-biphenyl-2-yl)dicyclohexylphosphine (X-PHOS, 38 mg) in dioxane (5 mL) bubbled with argon was added tris(dibenzylideneacetone)dipalladium Pd2(dba)3 (23 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 crystallized from ethyl acetate to give a pale yellow solid as 4-(4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperidin-1-yl)-benzoic acid tert-butyl ester (40 mg).

Workup

  1. custombubbled with argon
  2. additionwas added tris(dibenzylideneacetone)dipalladium Pd2(dba)3 (23 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 crystallized from ethyl acetate

Sources & evidence

ORD record
ord-236c63785a934e1589f3eacce8787581
Source dataset
uspto-grants-2012_07
Patent number
US08211914B2

Reaction notes

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