Triphenylarsine → (11beta,16alpha,17beta)-17-Cyclopropylcarbon-yl-16-methyl-11-[4-(3-pyridinyl)phenyl]estra-4,9-dien-3-one

HRID 638812노트

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HRID 638812 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:25][C@@:23]3([CH3:24])[C@@H:19]([CH2:20][C@@H:21]([CH3:31])[C@@H:22]3[C:26]([CH:28]3[CH2:30][CH2:29]3)=[O:27])[C@H:18]3[C:9]2=[C:10]2[C:15]([CH2:16][CH2:17]3)=[CH:14][C:13](=[O:32])[CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[N:33]1[CH:38]=[CH:37][CH:36]=[C:35](B(O)O)[CH:34]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:28]1([C:26]([C@H:22]2[C@H:21]([CH3:31])[CH2:20][C@H:19]3[C@H:18]4[C:9]([C@@H:8]([C:5]5[CH:4]=[CH:3][C:2]([C:35]6[CH:34]=[N:33][CH:38]=[CH:37][CH:36]=6)=[CH:7][CH:6]=5)[CH2:25][C@:23]23[CH3:24])=[C:10]2[C:15](=[CH:14][C:13](=[O:32])[CH2:12][CH2:11]2)[CH2:16][CH2:17]4)=[O:27])[CH2:29][CH2:30]1

참가 물질

8

반응물 4

HCID 11773TriphenylarsineHCID 62657Potassium Phosphate, TribasicHCID 27343783-Pyridinylboronic acidHCID 68576237(11beta,16alpha,17beta)-11-(4-Bromophenyl)-17-cyclopropylcarbonyl-16-methylestra-4,9-dien-3-one

생성물 1

HCID 11306419(11beta,16alpha,17beta)-17-Cyclopropylcarbon-yl-16-methyl-11-[4-(3-pyridinyl)phenyl]estra-4,9-dien-3-one수율 55.2%

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매2회HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

(11β,16α,17β)-11-(4-Bromophenyl)-17-cyclopropylcarbonyl-16-methylestra-4,9-dien-3-one (10 g, 20.3 mmol), 3-pyridinylboronic acid (3.7 g, 30.4 mmol), potassium phosphate (5.2 g, 24.3 mmol), bis(triphenylphosphine)palladium(II) chloride (442 mg, 0.61 mmol) and triphenylarsine (426 mg, 1.4 mmol) were dissolved in a mixture of dioxane (240 mL) and water (30 mL) under a nitrogen atmosphere. The reaction mixture was stirred for 2 hours at 100° C. and then cooled to room temperature. Water was added and the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4) and evaporated to dryness. Purification by column chromatography (SiO2, heptane/ethyl acetate, gradient 2/1 to 1/2) gave crude product (8.3 g, 16.9 mmol) which was crystallized from acetonitrile/water to give (11β,16α,17β)-17-cyclopropylcarbon-yl-16-methyl-11-[4-(3-pyridinyl)phenyl]estra-4,9-dien-3-one (5.5 g, 11.2 mmol, 55% yield), mp. 206° C. 1H NMR (400 MHz, CDCl3): δ 0.35 (s, 3H), 0.86-2.86 (m, 24H), 4.46 (d, J=8 Hz, 1H), 5.80 (s, 1H), 7.26-7.29 (m, 2H), 7.35 (dd, J=10 and 6 Hz, 1H), 7.49-7.53 (m, 2H), 7.86 (dt, J=10 and 4 Hz, 1H), 8.57 (dd, J=6 and 4 Hz, 1H), 8.84 (d, J=4 Hz, 1H).

후처리

  1. temperaturecooled to room temperature
  2. extractionthe mixture was extracted three times with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated to dryness
  6. customPurification by column chromatography (SiO2, heptane/ethyl acetate, gradient 2/1 to 1/2)
  7. customgave crude product (8.3 g, 16.9 mmol) which
  8. customwas crystallized from acetonitrile/water

출처 및 근거

ORD 기록
ord-7142e06c755d461aab65417da993b338
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07691836B2

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