Sodium Carbonate Monohydrate → HCID 86692314、化合物

HRID 1400973ノート

反応式

HRID 1400973 の反応式
FC(F)(F)S(O[C:7]1[C:8]([CH3:36])([CH3:35])[C@H:9]2[C@:22]([CH3:25])([CH2:23][CH:24]=1)[C@@H:21]1[C@:12]([CH3:34])([C@@:13]3([CH3:33])[C@H:18]([CH2:19][CH2:20]1)[C@H:17]1[C@H:26]([C:29]([CH3:31])=[CH2:30])[CH2:27][CH2:28][C@:16]1([NH2:32])[CH2:15][CH2:14]3)[CH2:11][CH2:10]2)(=O)=O.CC1(C)C(C)(C)OB([C:47]2[CH2:65][C:49]3([CH2:52][C:51]([C:59]([O:61][CH:62]([CH3:64])[CH3:63])=[O:60])([C:53]([O:55][CH:56]([CH3:58])[CH3:57])=[O:54])[CH2:50]3)[CH:48]=2)O1.O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:32][C@:16]12[CH2:28][CH2:27][C@@H:26]([C:29]([CH3:31])=[CH2:30])[C@@H:17]1[C@@H:18]1[C@@:13]([CH3:33])([CH2:14][CH2:15]2)[C@@:12]2([CH3:34])[C@@H:21]([C@:22]3([CH3:25])[C@@H:9]([CH2:10][CH2:11]2)[C:8]([CH3:36])([CH3:35])[C:7]([C:47]2[CH2:65][C:49]4([CH2:52][C:51]([C:59]([O:61][CH:62]([CH3:64])[CH3:63])=[O:60])([C:53]([O:55][CH:56]([CH3:57])[CH3:58])=[O:54])[CH2:50]4)[CH:48]=2)=[CH:24][CH2:23]3)[CH2:20][CH2:19]1

参加物

7

反応物 3

HCID 2735133Sodium Carbonate MonohydrateHCID 71698571(1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-3a-amino-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl trifluoromethanesulfonateHCID 86692315HCID 86692315、化合物

生成物 1

HCID 86692314HCID 86692314、化合物収率 66.4%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
85 °C

実験手順

To a vial containing (1R,3 aS,5aR,5bR,7aR,11aR,11bR,13 aR,13bR)-3a-amino-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl trifluoromethanesulfonate (1.54 g, 2.76 mmol) was added diisopropyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[3.3]hept-5-ene-2,2-dicarboxylate (1.044 g, 2.66 mmol), sodium carbonate monohydrate (0.856 g, 6.90 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.096 g, 0.083 mmol). The mixture was diluted with 1,4-dioxane (12 mL) and water (3 mL), then was flushed with nitrogen and the vial was sealed and heated to 85° C. After 5.5 h of heating, the mixture was cooled to rt. The mixture was diluted with water (40 mL) and extracted with dichloromethane (3×40 mL). The combined organic layers were dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography using a 0-50% ethyl acetate in hexanes gradient and a Thomson 80 g silica gel column. The fractions containing the expected product were combined and concentrated under reduced pressure to give diisopropyl 6-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)spiro[3.3]hept-5-ene-2,2-dicarboxylate (1.19 g, 1.766 mmol, 63.9% yield) as an off-white solid. LCMS: m/e 674.7 (M+H)+, 2.30 min (method 1). 1H NMR (500 MHz, chloroform-d) δ=5.87 (s, 1H), 5.52 (dd, J=6.4, 1.8 Hz, 1H), 5.13-5.01 (m, 2H), 4.73 (br. s., 1H), 4.61 (br. s., 1H), 2.74-2.66 (m, 4H), 2.63-2.51 (m, 3H), 2.14-1.99 (m, 2H), 1.70 (s, 3H), 1.27-1.23 (m, 12H), 1.15 (s, 3H), 1.07 (br. s., 3H), 1.06 (s, 3H), 0.97 (s, 3H), 0.83 (s, 3H), 1.76-0.80 (m, 20H).

後処理

  1. customwas flushed with nitrogen
  2. customthe vial was sealed
  3. temperatureAfter 5.5 h of heating
  4. temperaturethe mixture was cooled to rt
  5. additionThe mixture was diluted with water (40 mL)
  6. extractionextracted with dichloromethane (3×40 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. customThe drying agent was removed by filtration
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe residue was purified by flash chromatography
  11. additionThe fractions containing the expected product
  12. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-dbb87a4986e945cca4833c3c6c3538e1
出典データセット
uspto-grants-2014_12
特許番号
US08906889B2

反応ノート

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