Trifluoroacetic acid → Trifluoroacetic acid

HRID 338642Notes

Reaction equation

HRID 338642 reaction equation
[CH3:1][C@:2]12[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:32])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:22])([CH3:21])[C:14]([C:23]3[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=3)=[CH:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:33]([C:36]([CH3:38])=[CH2:37])[CH2:34][CH2:35][C@:5]1([NH:39][CH2:40][CH2:41][N:42]1[CH2:47][C@@H:46]3[CH2:48][C@H:43]1[CH2:44][N:45]3[S:49]([CH3:52])(=[O:51])=[O:50])[CH2:4][CH2:3]2.[C:53]([OH:59])([C:55]([F:58])([F:57])[F:56])=[O:54]>C1COCC1.CO.[OH-].[OH-].[Pd+2]>[CH:36]([C@H:33]1[C@@H:6]2[C@@H:7]3[C@@:2]([CH3:1])([CH2:3][CH2:4][C@@:5]2([NH:39][CH2:40][CH2:41][N:42]2[CH2:47][C@@H:46]4[CH2:48][C@H:43]2[CH2:44][N:45]4[S:49]([CH3:52])(=[O:50])=[O:51])[CH2:35][CH2:34]1)[C@@:19]1([CH3:20])[C@@H:10]([C@:11]2([CH3:32])[C@@H:16]([CH2:17][CH2:18]1)[C:15]([CH3:21])([CH3:22])[C:14]([C:23]1[CH:24]=[CH:25][C:26]([C:27]([OH:29])=[O:28])=[CH:30][CH:31]=1)=[CH:13][CH2:12]2)[CH2:9][CH2:8]3)([CH3:38])[CH3:37].[C:53]([OH:59])([C:55]([F:58])([F:57])[F:56])=[O:54]

Participants

7

Reactant 2

HCID 6422Trifluoroacetic acidHCID 72203051HCID 72203051, compound

Product 2

HCID 6422Trifluoroacetic acidYield 60.6%HCID 72203184HCID 72203184, compound

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-((1S,4S)-5-(methylsulfonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)ethyl)amino)-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, 2 TFA (10 mg, 10.42 μmol) in a mixture of THF (1.5 mL) and MeOH (0.5 mL) was added palladium hydroxide on carbon (14.63 mg, 0.021 mmol). The resulting slurry was purged with H2 (g) and stirred under a H2 (g) atmosphere for 16 h. The mixture was treated with celite (15 mg), filtered, washed with THF and concentrated. A grey residue was dissolved in THF (1 mL) and MeOH (0.5 mL), purified by reverse phase prep-HPLC using HPLC methods 6 and dried under vacuum to give 4-((1S,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-3a-((2-((1S,4S)-5-(methylsulfonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)ethyl)amino)-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, 2 TFA (6.2 mg, 60.6% yield) as white solid. LC/MS: m/e 734.6 (M+H)+, 2.25 min (method 3). 1H NMR (400 MHz, 1:1 CDCl3:METHANOL-d4) δ 7.91 (d, J=8.3 Hz, 2H), 7.19 (d, J=8.3 Hz, 2H), 5.29 (d, J=4.6 Hz, 1H), 4.35 (s, 1H), 3.82 (s, 1H), 3.61 (d, J=10.3 Hz, 1H), 3.28 (d, J=1.7 Hz, 1H), 3.15 (d, J=11.7 Hz, 1H), 3.10-3.00 (m, 3H), 2.92 (s, 3H), 2.82 (d, J=10.0 Hz, 1H), 2.14 (dd, J=17.1, 6.4 Hz, 1H), 2.09-2.03 (m, 1H), 2.02-1.86 (m, 5H), 1.85-1.64 (m, 7H), 1.57 (dd, J=17.4, 11.7 Hz, 5H), 1.51-1.40 (m, 4H), 1.39-1.21 (m, 4H), 1.15 (s, 3H), 1.07 (s, 3H), 1.02 (s, 3H), 0.94 (s, 3H), 0.93 (s, 3H), 0.90 (d, J=6.8 Hz, 3H), 0.81 (d, J=6.6 Hz, 3H).

Workup

  1. customThe resulting slurry was purged with H2 (g)
  2. additionThe mixture was treated with celite (15 mg)
  3. filtrationfiltered
  4. washwashed with THF
  5. concentrationconcentrated
  6. dissolutionA grey residue was dissolved in THF (1 mL)
  7. customMeOH (0.5 mL), purified by reverse phase
  8. customdried under vacuum

Sources & evidence

ORD record
ord-28612e60a082478680d3dcdea3f9b815
Source dataset
uspto-grants-2014_11
Patent number
US08889854B2

Reaction notes

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