Phosphoric Acid → (S)-benzyl 4-((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)cyclohex-3-enecarboxylate

HRID 1400992ノート

反応式

HRID 1400992 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.P(=O)(O)(O)O.[K].CC1(C)C(C)(C)OB([C:53]2[CH2:58][CH2:57][C@H:56]([C:59]([O:61][CH2:62][C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)=[O:60])[CH2:55][CH:54]=2)O1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[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:53]2[CH2:58][CH2:57][C@H:56]([C:59]([O:61][CH2:62][C:63]4[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=4)=[O:60])[CH2:55][CH:54]=2)=[CH:24][CH2:23]3)[CH2:20][CH2:19]1

参加物

9

反応物 5

HCID 1004Phosphoric AcidHCID 5462222PotassiumHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 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 86692349(S)-benzyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-enecarboxylate

生成物 1

HCID 86692348(S)-benzyl 4-((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)cyclohex-3-enecarboxylate収率 75%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
75 °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 (0.05 g, 0.090 mmol) was added phosphoric acid, potassium salt (0.057 g, 0.269 mmol), (S)-benzyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-enecarboxylate (0.062 g, 0.181 mmol) (enantiomer 2 prepared above), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (S-phos) (5.52 mg, 0.013 mmol), and palladium(II) acetate (2.013 mg, 8.96 mmol). The mixture was diluted with 1,4-dioxane (1 mL) and water (0.1 mL), was flushed with nitrogen, then was sealed and heated to 75° C. After 6 h of heating, the mixture was cooled to rt, was diluted with dichloromethane, and was dried with 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 10-60% ethyl acetate in hexanes gradient and a 12 g silica gel column. The fractions containing the expected product were combined and concentrated under reduced pressure to give (S)-benzyl 4-((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)cyclohex-3-enecarboxylate (0.042 g, 0.067 mmol, 75% yield) as an off-white solid. 1H NMR (500 MHz, chloroform-d) δ=7.42-7.31 (m, 5H), 5.37 (br. s., 1H), 5.21-5.17 (m, 1H), 5.16 (s, 2H), 4.75 (d, J=1.9 Hz, 1H), 4.62 (s, 1H), 2.65-2.52 (m, 2H), 2.39-2.32 (m, 2H), 2.22-2.15 (m, 2H), 2.10-1.96 (m, 3H), 1.71 (s, 3H), 1.09 (s, 3H), 0.98 (s, 6H), 0.91 (s, 3H), 0.88 (s, 3H), 1.82-0.83 (m, 23H).

後処理

  1. customwas flushed with nitrogen
  2. customwas sealed
  3. temperatureAfter 6 h of heating
  4. temperaturethe mixture was cooled to rt
  5. additionwas diluted with dichloromethane
  6. dry with materialwas dried with sodium sulfate
  7. customThe drying agent was removed by filtration
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by flash chromatography
  10. additionThe fractions containing the expected product
  11. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-7dcb264fe0d549128f9f0c814a8c7f2e
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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