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 1510293노트

반응식

HRID 1510293 반응식
[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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

반응 조건

온도
105 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-236c63785a934e1589f3eacce8787581
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08211914B2

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