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

HRID 638812ノート

反応式

HRID 638812 の反応式
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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒2 回HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

(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).

後処理

  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

出典と根拠

ORDレコード
ord-7142e06c755d461aab65417da993b338
出典データセット
uspto-grants-2010_04
特許番号
US07691836B2

反応ノート

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