Sodium Carbonate Monohydrate → methyl 6-((1R,3 aS,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-carboxylate

HRID 1400974ノート

反応式

HRID 1400974 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[CH2:57][C:49]3([CH2:52][CH:51]([C:53]([O:55][CH3:56])=[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]([CH3:35])([CH3:36])[C:7]([C:47]2[CH2:57][C:49]4([CH2:50][CH:51]([C:53]([O:55][CH3:56])=[O:54])[CH2:52]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 86692319Methyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[3.3]hept-5-ene-2-carboxylate

生成物 1

HCID 86692318methyl 6-((1R,3 aS,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-carboxylate収率 74%

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,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 trifluoromethanesulfonate (0.418 g, 0.749 mmol) was added methyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[3.3]hept-5-ene-2-carboxylate (0.250 g, 0.899 mmol), sodium carbonate monohydrate (0.232 g, 1.874 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.026 g, 0.022 mmol). The mixture was diluted with 1,4-dioxane (4 mL) and water (1 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, concentrated under reduced pressure, adsorbed to silica gel, and purified by chromatography using a 0-45% ethyl acetate in hexanes gradient and a 40 g Thomson silica gel column. The fractions containing the expected product were combined and concentrated under reduced pressure to give methyl 6-((1R,3 aS,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-carboxylate (0.31 g, 0.554 mmol, 73.9% yield) as an off-white solid. 1H NMR showed a mixture of the two diastereomers (0.8:1 ratio) which were not separated and were used in the next step with no additional purification. LCMS: m/e 560.47 (M+H)+, 2.46 min (method 2). Mixture of diastereomers: 1H NMR (500 MHz, chloroform-d) δ=6.00 (s, 0.45H, minor diastereomer), 5.84 (s, 0.55H, major diastereomer), 5.54 (td, J=6.1, 2.2 Hz, 1H), 4.75 (d, J=2.0 Hz, 1H), 4.62 (dd, J=2.3, 1.3 Hz, 1H), 3.71 (m, 3H), 3.13-2.99 (m, 1H), 2.70-2.31 (m, 7H), 2.18-1.84 (m, 4H), 1.72 (s, 3H), 1.18 (d, J=3.5 Hz, 3H), 1.10-1.08 (m, 6H), 0.99 (s, 3H), 0.85 (s, 3H), 1.68-0.83 (m, 19H).

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. concentrationconcentrated under reduced pressure
  6. custompurified by chromatography
  7. additionThe fractions containing the expected product
  8. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-b94ea3e7da534b70954c05c34a04ea44
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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