Trifluoroacetic acid → 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(3-(dimethylamino)propanamido)-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

HRID 85569Notes

Reaction equation

HRID 85569 reaction equation
[CH3:1][N:2]([CH3:47])[CH2:3][CH2:4][C:5]([NH:7][C@:8]12[CH2:43][CH2:42][C@@H:41]([C:44]([CH3:46])=[CH2:45])[C@@H:9]1[C@@H:10]1[C@@:23]([CH3:26])([CH2:24][CH2:25]2)[C@@:22]2([CH3:27])[C@@H:13]([C@:14]3([CH3:40])[C@@H:19]([CH2:20][CH2:21]2)[C:18]([CH3:29])([CH3:28])[C:17]([C:30]2[CH:39]=[CH:38][C:33]([C:34]([O:36]C)=[O:35])=[CH:32][CH:31]=2)=[CH:16][CH2:15]3)[CH2:12][CH2:11]1)=[O:6].C(O)(C(F)(F)F)=O.O.[OH-].[Li+]>C1COCC1.O>[CH3:47][N:2]([CH3:1])[CH2:3][CH2:4][C:5]([NH:7][C@:8]12[CH2:43][CH2:42][C@@H:41]([C:44]([CH3:46])=[CH2:45])[C@@H:9]1[C@@H:10]1[C@@:23]([CH3:26])([CH2:24][CH2:25]2)[C@@:22]2([CH3:27])[C@@H:13]([C@:14]3([CH3:40])[C@@H:19]([CH2:20][CH2:21]2)[C:18]([CH3:29])([CH3:28])[C:17]([C:30]2[CH:31]=[CH:32][C:33]([C:34]([OH:36])=[O:35])=[CH:38][CH:39]=2)=[CH:16][CH2:15]3)[CH2:12][CH2:11]1)=[O:6]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 168937Lithium hydroxide, monohydrateHCID 68358011methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(3-(dimethylamino)propanamido)-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

Product 1

HCID 683578604-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(3-(dimethylamino)propanamido)-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 acidYield 67.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(3-(dimethylamino)propanamido)-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 (87.9 mg, 0.116 mmol) in THF (5 mL) was added a solution of lithium hydroxide monohydrate (19.49 mg, 0.464 mmol) in water (1.00 mL). The reaction was stirred at 75° C. After 8 h, the reaction was concentrated to dryness. The crude material was dissolved in THF (1 mL) and MeOH (1.5 mL), filtered and purified by reverse phase preparative HPLC using HPLC method 1 to give the title compound (59.5 mg, 0.078 mmol, 67.6% yield) as a white solid. LCMS: m/e 629.4 (M+H)+, 4.17 min (method 8). 1H NMR (500 MHz, METHANOL-d4) δ=7.95 (d, J=8.2 Hz, 2H), 7.24 (d, J=8.2 Hz, 3H), 5.33 (dd, J=1.5, 6.1 Hz, 1H), 4.80 (d, J=1.5 Hz, 1H), 4.67 (s, 1H), 3.40 (t, J=6.6 Hz, 2H), 2.92 (s, 6H), 2.88-2.69 (m, 4H), 2.42 (dd, J=8.4, 12.4 Hz, 1H), 2.18 (dd, J=6.4, 17.1 Hz, 1H), 2.05-1.89 (m, 2H), 1.83 (d, J=11.3 Hz, 1H), 1.79-1.76 (m, 1H), 1.75 (s, 3H), 1.74-1.71 (m, 1H), 1.66-1.56 (m, 3H), 1.56-1.49 (m, 4H), 1.47-1.28 (m, 5H), 1.22-1.17 (m, 1H), 1.16 (s, 3H), 1.15-1.10 (m, 1H), 1.07 (s, 6H), 0.99 (s, 3H), 0.97 (s, 3H). 13C NMR (MeOD) δ ppm 14.5, 16.1, 16.8, 19.1, 20.6, 21.3, 22.1, 26.2, 28.2, 29.4, 29.7, 30.4, 34.5, 35.5, 37.1, 38.1, 38.2, 41.5, 42.5, 42.8, 43.2, 47.6, 49.3, 50.1, 50.5, 54.0, 55.1, 66.4, 110.4, 124.9, 129.5, 130.9, 147.4, 149.6, 150.8, 169.6, 171.0.

Workup

  1. concentrationthe reaction was concentrated to dryness
  2. dissolutionThe crude material was dissolved in THF (1 mL)
  3. filtrationMeOH (1.5 mL), filtered
  4. custompurified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-83a7634874474fd1b589cd989dffc4bc
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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