Trifluoroacetic acid → 4-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(aminomethyl)-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 405101Notes

Reaction equation

HRID 405101 reaction equation
[NH2:1][CH2:2][C@:3]12[CH2:41][CH2:40][C@@H:39]([C:42]([CH3:44])=[CH2:43])[C@@H:4]1[C@@H:5]1[C@@:18]([CH3:21])([CH2:19][CH2:20]2)[C@@:17]2([CH3:22])[C@@H:8]([C@:9]3([CH3:38])[C@@H:14]([CH2:15][CH2:16]2)[C:13]([CH3:24])([CH3:23])[C:12]([C:25]2[CH:37]=[CH:36][C:28]([C:29]([O:31]C(C)(C)C)=[O:30])=[CH:27][CH:26]=2)=[CH:11][CH2:10]3)[CH2:7][CH2:6]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:1][CH2:2][C@:3]12[CH2:41][CH2:40][C@@H:39]([C:42]([CH3:44])=[CH2:43])[C@@H:4]1[C@@H:5]1[C@@:18]([CH3:21])([CH2:19][CH2:20]2)[C@@:17]2([CH3:22])[C@@H:8]([C@:9]3([CH3:38])[C@@H:14]([CH2:15][CH2:16]2)[C:13]([CH3:24])([CH3:23])[C:12]([C:25]2[CH:37]=[CH:36][C:28]([C:29]([OH:31])=[O:30])=[CH:27][CH:26]=2)=[CH:11][CH2:10]3)[CH2:7][CH2:6]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86676419tert-butyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(aminomethyl)-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 715977424-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(aminomethyl)-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 88.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(aminomethyl)-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 (15 mg, 0.025 mmol) in DCM (4 mL) was added TFA (0.4 ml, 5.19 mmol) and the mixture was stirred at room temperature. The color of the solution turned pinkish. After 6 h, the solvent was removed in vacuo and the crude was purified by reverse phase prep. HPLC to afford the title compound as a white foam (12 mg, 80%). LCMS: m/e 544.49 (MH+), 2.60 min (method 3). 1H NMR (500 MHz, MeOD) δ ppm 7.94 (2H, d, J=8.5 Hz), 7.24 (2H, d, J=8.5 Hz), 5.32 (1H, dd, J=6.3, 1.7 Hz), 4.77 (1H, d, J=1.8 Hz), 4.66 (1H, s), 3.10-3.24 (1H, m), 2.73-2.84 (1H, m), 2.50 (1H, td, J=10.6, 5.6 Hz), 2.17 (1H, dd, J=17.1, 6.4 Hz), 1.98-2.11 (1H, m), 1.67-1.89 (8H, m), 1.54-1.66 (3H, m), 1.44-1.56 (5H, m), 1.33-1.45 (2H, m), 1.27-1.34 (3H, m), 1.23-1.28 (1H, m), 1.15-1.24 (4H, m), 1.11 (3H, s), 1.06 (3H, s), 0.92-1.02 (6H, m).

Workup

  1. customthe solvent was removed in vacuo
  2. customthe crude was purified by reverse phase prep

Sources & evidence

ORD record
ord-8525e7bba6d54781bc66852f01799b47
Source dataset
uspto-grants-2014_06
Patent number
US08748415B2

Reaction notes

Loading…