Lithium Hydroxide → Trifluoroacetic acid

HRID 338643Notes

Reaction equation

HRID 338643 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([CH3:57])([CH3:56])[C@H:13]3[C@:26]([CH3:29])([CH2:27][CH:28]=2)[C@@H:25]2[C@:16]([CH3:55])([C@@:17]4([CH3:54])[C@H:22]([CH2:23][CH2:24]2)[C@H:21]2[C@H:30]([C:33]([CH3:35])=[CH2:34])[CH2:31][CH2:32][C@:20]2([NH:36][CH2:37][CH2:38][N:39]2[CH2:45][C@H:44]5[N:46]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[C@H:41]([CH2:42][CH2:43]5)[CH2:40]2)[CH2:19][CH2:18]4)[CH2:15][CH2:14]3)=[CH:7][CH:6]=1)=[O:4].[C:58]([OH:64])([C:60]([F:63])([F:62])[F:61])=[O:59].[OH-].[Li+]>C1COCC1.CO>[C:50]([O:49][C:47]([N:46]1[C@H:41]2[CH2:42][CH2:43][C@@H:44]1[CH2:45][N:39]([CH2:38][CH2:37][NH:36][C@:20]13[CH2:32][CH2:31][C@@H:30]([C:33]([CH3:35])=[CH2:34])[C@@H:21]1[C@@H:22]1[C@@:17]([CH3:54])([CH2:18][CH2:19]3)[C@@:16]3([CH3:55])[C@@H:25]([C@:26]4([CH3:29])[C@@H:13]([CH2:14][CH2:15]3)[C:12]([CH3:57])([CH3:56])[C:11]([C:8]3[CH:7]=[CH:6][C:5]([C:3]([OH:4])=[O:2])=[CH:10][CH:9]=3)=[CH:28][CH2:27]4)[CH2:24][CH2:23]1)[CH2:40]2)=[O:48])([CH3:51])([CH3:52])[CH3:53].[C:58]([OH:64])([C:60]([F:63])([F:62])[F:61])=[O:59]

Participants

7

Reactant 3

HCID 3939Lithium HydroxideHCID 6422Trifluoroacetic acidHCID 86701806HCID 86701806, compound

Product 2

HCID 6422Trifluoroacetic acidYield 69%HCID 86701805HCID 86701805, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of (1R,5S)-tert-butyl 3-(2-(((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(4-(methoxycarbonyl)phenyl)-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-3a-yl)amino)ethyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate, 2 TFA (30 mg, 0.030 mmol) in THF (0.75 mL) and MeOH (0.25 mL) was added a solution of lithium hydroxide (1N) (0.148 mL, 0.148 mmol). The reaction mixture was stirred at 75° C. After 1 h, the reaction mixture was cooled to rt and purified by reverse phase prep-HPLC using HPLC method 7 and dried to give 4-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-((1R,5S)-8-(tert-butoxycarbonyl)-3,8-diazabicyclo[3.2.1]octan-3-yl)ethyl)amino)-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, 2 TFA (22.2 mg, 0.021 mmol, 69.0% yield) as pale yellow solid. LC/MS: m/e 768.8 (M+H)+, 2.34 min (method 3). 1H NMR (400 MHz, CHLOROFORM-d) δ 7.96 (d, J=8.1 Hz, 2H), 7.21 (d, J=8.3 Hz, 2H), 5.13 (d, J=5.4 Hz, 1H), 4.84 (br. s., 1H), 4.68 (s, 1H), 4.36 (br. s., 2H), 3.68-3.32 (m, 6H), 2.98 (d, J=10.3 Hz, 2H), 2.70 (br. s., 1H), 2.08 (br. s., 7H), 1.97-1.82 (m, 2H), 1.70 (d, J=5.9 Hz, 1H), 1.66 (s, 3H), 1.63-1.51 (m, 5H), 1.49 (s, 9H), 1.47-1.39 (m, 5H), 1.39-1.27 (m, 4H), 1.27-1.15 (m, 3H), 1.11 (s, 3H), 1.02 (s, 3H), 0.98 (s, 3H), 0.97-0.94 (m, 3H), 0.89 (s, 4H).

Workup

  1. temperaturethe reaction mixture was cooled to rt
  2. custompurified by reverse phase
  3. customdried

Sources & evidence

ORD record
ord-49a1bb28ab454d6bb07f8a925b5baa29
Source dataset
uspto-grants-2014_11
Patent number
US08889854B2

Reaction notes

Loading…