Trifluoroacetic acid → Trifluoroacetic acid

HRID 85611ノート

反応式

HRID 85611 の反応式
[F:1][C:2]1[CH:7]=[C:6]([CH2:8][NH:9][C@:10]23[CH2:45][CH2:44][C@@H:43]([C:46]([CH3:48])=[CH2:47])[C@@H:11]2[C@@H:12]2[C@@:25]([CH3:28])([CH2:26][CH2:27]3)[C@@:24]3([CH3:29])[C@@H:15]([C@:16]4([CH3:42])[C@@H:21]([CH2:22][CH2:23]3)[C:20]([CH3:31])([CH3:30])[C:19]([C:32]3[CH:41]=[CH:40][C:35]([C:36]([O:38]C)=[O:37])=[CH:34][CH:33]=3)=[CH:18][CH2:17]4)[CH2:14][CH2:13]2)[CH:5]=[CH:4][N:3]=1.[C:49]([OH:55])([C:51]([F:54])([F:53])[F:52])=[O:50].O[Li].O>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([CH2:8][NH:9][C@:10]23[CH2:45][CH2:44][C@@H:43]([C:46]([CH3:48])=[CH2:47])[C@@H:11]2[C@@H:12]2[C@@:25]([CH3:28])([CH2:26][CH2:27]3)[C@@:24]3([CH3:29])[C@@H:15]([C@:16]4([CH3:42])[C@@H:21]([CH2:22][CH2:23]3)[C:20]([CH3:31])([CH3:30])[C:19]([C:32]3[CH:41]=[CH:40][C:35]([C:36]([OH:38])=[O:37])=[CH:34][CH:33]=3)=[CH:18][CH2:17]4)[CH2:14][CH2:13]2)[CH:5]=[CH:4][N:3]=1.[C:49]([OH:55])([C:51]([F:54])([F:53])[F:52])=[O:50]

参加物

6

反応物 3

HCID 6422Trifluoroacetic acidHCID 168937Lithium hydroxide, monohydrateHCID 68358208methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-fluoropyridin-4-yl)methylamino)-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)benzoate

生成物 2

HCID 6422Trifluoroacetic acid収率 36.1%HCID 683582074-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-fluoropyridin-4-yl)methylamino)-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)benzoic acid

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
75 °C

実験手順

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-fluoropyridin-4-yl)methylamino)-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)benzoate, TFA (77.7 mg, 0.101 mmol) in THF (3 mL) was added a 0.753 molar aqueous solution of LiOH.H2O (0.539 mL, 0.405 mmol). The reaction mixture was heated to 75° C. After 4 h, the reaction mixture was concentrated. The crude residue was dissolved in THF (1.5 mL) and MeOH (200 μL), filtered and purified by reverse phase preparative HPLC using HPLC method 3 to give 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-fluoropyridin-4-yl)methylamino)-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)benzoic acid, TFA (30.6 mg, 0.037 mmol, 36.1% yield) as a white solid. LCMS: m/e 637.7 (M−H)−, 3.12 min (method 6). 1H NMR (500 MHz, 1:1 CDCl3:MeOD) δ=8.24 (d, J=5.2 Hz, 1H), 7.92 (d, J=8.2 Hz, 2H), 7.43 (d, J=5.2 Hz, 1H), 7.24 (s, 1H), 7.20 (d, J=8.5 Hz, 2H), 5.29 (dd, J=1.7, 6.3 Hz, 1H), 4.78 (s, 1H), 4.17 (br. s., 2H), 2.78-2.69 (m, 1H), 2.18-2.10 (m, 2H), 2.09-2.01 (m, 2H), 1.98 (dd, J=3.1, 11.9 Hz, 1H), 1.96-1.88 (m, 1H), 1.83-1.76 (m, 1H), 1.72 (s, 3H), 1.70-1.64 (m, 1H), 1.63-1.40 (m, 10H), 1.39-1.31 (m, 1H), 1.31-1.23 (m, 2H), 1.13 (s, 3H), 1.07 (s, 3H), 1.02 (s, 3H), 0.95 (s, 3H), 0.94 (s, 3H). 13C NMR (1:1 CDCl3:MeOD) d ppm 15.3, 16.6, 17.4, 19.5, 20.6, 21.8, 22.2, 26.1, 27.6, 29.0, 29.5, 30.2, 33.9, 34.6, 37.2, 38.2, 38.4, 41.8, 42.8, 43.1, 45.7, 47.2, 49.7, 49.9, 50.3, 50.5, 53.9, 78.8, 123.1, 123.2, 124.9, 129.3, 129.7, 131.0, 147.4, 149.7, 164.0, 166.0, 170.1.

後処理

  1. concentrationthe reaction mixture was concentrated
  2. dissolutionThe crude residue was dissolved in THF (1.5 mL)
  3. filtrationMeOH (200 μL), filtered
  4. custompurified by reverse phase preparative HPLC

出典と根拠

ORDレコード
ord-09171b72b3554738bf5b0a7ea46aac0b
出典データセット
uspto-grants-2014_09
特許番号
US08846647B2

反応ノート

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