Water → Methyl 3-(3,6-dihydro-2H-pyran-4-yl)-4-(tetrahydro-2H-pyran-2-yloxy)benzoate

HRID 1662432노트

반응식

HRID 1662432 반응식
C1([C@H](C2C=CC=[C:11]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20](C4C=C(OC)C=CC=4F)=[C:19]([C@@H:32]4[CH2:36][CH2:35]C[C:33]4([CH3:38])C)[CH:18]=3)C=2)CC(O)=O)CC1.C[O:40][C:41]1[CH:42]=[CH:43][CH:44]=[C:45]([O:66]C)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[O-:68]P([O-])([O-])=O.[K+].[K+].[K+].[OH2:76]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:76]1[CH2:38][CH:33]=[C:32]([C:19]2[CH:18]=[C:17]([CH:22]=[CH:21][C:20]=2[O:66][CH:45]2[CH2:44][CH2:43][CH2:42][CH2:41][O:40]2)[C:16]([O:15][CH3:11])=[O:68])[CH2:36][CH2:35]1

참가 물질

7

반응물 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 57706097(3r)-3-Cyclopropyl-3-(3-(((2-((1r)-2,2-dimethylcyclopentyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)phenyl)propanoic acid

생성물 1

HCID 57706658Methyl 3-(3,6-dihydro-2H-pyran-4-yl)-4-(tetrahydro-2H-pyran-2-yloxy)benzoate수율 52%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매

반응 조건

온도
75 °C

실험 절차

A stirred mixture of 66.6 F (1.40 g, 4.45 mmol), ground S-Phos (0.38 g, 0.920 mmol), palladium acetate (0.11 g, 0.475 mmol), 66.46B (1.40 g, 6.65 mmol), and potassium phosphate tribasic (2.48 g, 11.7 mmol) in DMF (10.0 mL) and water (0.5 mL) was purged three times with argon. The mixture was heated to 75° C. and monitored with LC-MS. After 21 hours, the reaction was cooled to room temperature and then diluted with water and extracted three times with EtOAc. The organic layers were combined and washed twice with brine. After drying over anhydrous sodium sulfate and filtration, the organic solvent was removed under reduced pressure. The residue was purified on silica gel using 0-20% EtOAc in hexanes to afford 66.46C as a colorless oil (0.73 g, 52% yield). MS ESI (pos.) m/e: 340.9 (M+Na)+.

후처리

  1. customwas purged three times with argon
  2. temperaturethe reaction was cooled to room temperature
  3. additiondiluted with water
  4. extractionextracted three times with EtOAc
  5. washwashed twice with brine
  6. dry with materialAfter drying over anhydrous sodium sulfate and filtration
  7. customthe organic solvent was removed under reduced pressure
  8. customThe residue was purified on silica gel using 0-20% EtOAc in hexanes

출처 및 근거

ORD 기록
ord-4236fb732c7c476d92fac32f2a9d761e
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08030354B2

반응 노트

불러오는 중…