Trifluoroacetic acid → 4-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-[[2-dimethylaminoethyl-(3-hydroxy-3-oxo-propanoyl)amino]methyl]-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysen-9-yl]benzoic acid

HRID 405071Notes

Reaction equation

HRID 405071 reaction equation
C([O:5][C:6](=[O:59])[CH2:7][C:8]([N:10]([CH2:16][C@:17]12[CH2:55][CH2:54][C@@H:53]([C:56]([CH3:58])=[CH2:57])[C@@H:18]1[C@@H:19]1[C@@:32]([CH3:35])([CH2:33][CH2:34]2)[C@@:31]2([CH3:36])[C@@H:22]([C@:23]3([CH3:52])[C@@H:28]([CH2:29][CH2:30]2)[C:27]([CH3:38])([CH3:37])[C:26]([C:39]2[CH:51]=[CH:50][C:42]([C:43]([O:45]C(C)(C)C)=[O:44])=[CH:41][CH:40]=2)=[CH:25][CH2:24]3)[CH2:21][CH2:20]1)[CH2:11][CH2:12][N:13]([CH3:15])[CH3:14])=[O:9])(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[C:6]([CH2:7][C:8]([N:10]([CH2:16][C@:17]12[CH2:55][CH2:54][C@@H:53]([C:56]([CH3:58])=[CH2:57])[C@@H:18]1[C@@H:19]1[C@@:32]([CH3:35])([CH2:33][CH2:34]2)[C@@:31]2([CH3:36])[C@@H:22]([C@:23]3([CH3:52])[C@@H:28]([CH2:29][CH2:30]2)[C:27]([CH3:38])([CH3:37])[C:26]([C:39]2[CH:40]=[CH:41][C:42]([C:43]([OH:45])=[O:44])=[CH:50][CH:51]=2)=[CH:25][CH2:24]3)[CH2:21][CH2:20]1)[CH2:11][CH2:12][N:13]([CH3:15])[CH3:14])=[O:9])([OH:59])=[O:5]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86676409tert-butyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((3-tert-butoxy-N-(2-(dimethylamino)ethyl)-3-oxopropanamido)methyl)-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 715964874-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-[[2-dimethylaminoethyl-(3-hydroxy-3-oxo-propanoyl)amino]methyl]-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysen-9-yl]benzoic acidYield 56.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((3-tert-butoxy-N-(2-(dimethylamino)ethyl)-3-oxopropanamido)methyl)-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 (31 mg, 0.038 mmol) in dichloromethane (1 ml) was added TFA (0.25 ml, 3.24 mmol). The mixture was stirred at rt for 3 h then was concentrated under reduced pressure. The residue was purified by prep HPLC. The fractions containing the expected product were combined and concentrated under reduced pressure to afford 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-carboxy-N-(2-(dimethylamino)ethyl)acetamido)methyl)-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 as a white solid (15 mg, 0.021 mmol, 56.1% yield). LCMS: m/e 701.5 (M+H)+, 2.11 min (method 6). 1H NMR (500 MHz, Acetic acid-d3 acid-d) δ ppm 8.04 (d, J=8.24 Hz, 2H), 7.31 (d, J=8.24 Hz, 2H), 5.38 (d, J=5.19 Hz, 1H), 4.85 (d, J=16.17 Hz, 1H), 4.69 (d, J=15.56 Hz, 1H), 3.86-4.13 (m, 2H), 2.97-3.82 (m, 6H), 2.62-2.73 (m, 1H), 2.13-2.24 (m, 2H), 1.06-1.92 (m, 38H), 1.03 (s, 3H), 1.01 (s, 3H).

Workup

  1. concentrationthen was concentrated under reduced pressure
  2. customThe residue was purified by prep HPLC
  3. additionThe fractions containing the expected product
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8fcf456288ed4a03bfb36e3b4cf95201
Source dataset
uspto-grants-2014_06
Patent number
US08748415B2

Reaction notes

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