Trifluoroacetic acid → Trifluoroacetic acid

HRID 85607Notes

Reaction equation

HRID 85607 reaction equation
[O:1]=[S:2]1(=[O:50])[CH2:7][CH2:6][N:5]([CH2:8][C:9]([NH:11][C:12]23[CH2:46][CH2:45][C@@H:44]([CH:47]([CH3:49])[CH3:48])[C@@H:13]2[C@@H:14]2[C@@:27]([CH3:30])([CH2:28][CH2:29]3)[C@@:26]3([CH3:31])[C@@H:17]([C@:18]4([CH3:43])[C@@H:23]([CH2:24][CH2:25]3)[C:22]([CH3:33])([CH3:32])[C@@H:21]([C:34]3[CH:42]=[CH:41][C:37]([C:38]([O-:40])=[O:39])=[CH:36][CH:35]=3)[CH2:20][CH2:19]4)[CH2:16][CH2:15]2)=[O:10])[CH2:4][CH2:3]1.[C:51]([OH:57])([C:53]([F:56])([F:55])[F:54])=[O:52].O.[OH-].[Li+]>C1COCC1>[O:50]=[S:2]1(=[O:1])[CH2:7][CH2:6][N:5]([CH2:8][C:9]([NH:11][C@:12]23[CH2:46][CH2:45][C@@H:44]([CH:47]([CH3:48])[CH3:49])[C@@H:13]2[C@@H:14]2[C@@:27]([CH3:30])([CH2:28][CH2:29]3)[C@@:26]3([CH3:31])[C@@H:17]([C@:18]4([CH3:43])[C@@H:23]([CH2:24][CH2:25]3)[C:22]([CH3:33])([CH3:32])[C@@H:21]([C:34]3[CH:35]=[CH:36][C:37]([C:38]([OH:40])=[O:39])=[CH:41][CH:42]=3)[CH2:20][CH2:19]4)[CH2:16][CH2:15]2)=[O:10])[CH2:4][CH2:3]1.[C:51]([OH:57])([C:53]([F:56])([F:55])[F:54])=[O:52]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 168937Lithium hydroxide, monohydrateHCID 86676582HCID 86676582, compound

Product 2

HCID 6422Trifluoroacetic acidYield 69.1%HCID 683581294-((1S,3aS,5aR,5bR,7aS,9S,11aS,11bR,13aR,13bR)-3a-(((1,1-dioxido-4-thiomorpholinyl)acetyl)amino)-1-isopropyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 4-[(1S,5aR,5bR,7aS,9S,11aS,11bR,13aR,13bR)-3a-[[2-(1,1-dioxo-1,4-thiazinan-4-yl)acetyl]amino]-1-isopropyl-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-yl]benzoate, TFA (24.3 mg, 0.029 mmol) in THF (3 mL) was added a 0.753 molar aqueous solution of lithium hydroxide monohydrate (0.232 mL, 0.116 mmol). The reaction mixture was heated to 75° C. After 5.5 h, the reaction mixture was concentrated to dryness. The crude residue was dissolved in THF (1.2 mL), MeOH (0.3 mL) and 1N HCl (0.2 mL). The resulting solution was filtered and purified using prep HPLC method 3 to give 4-((1S,3aS,5aR,5bR,7aS,9S,11aS,11bR,13aR,13bR)-3a-(((1,1-dioxido-4-thiomorpholinyl)acetyl)amino)-1-isopropyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid, TFA (16.5 mg, 0.020 mmol, 69.1% yield) as a white solid. LCMS: m/z 709.6 (M+H+), retention time 2.072 min (method 6). 1H NMR (500 MHz, METHANOL-d4) δ=7.91 (d, J=8.2 Hz, 2H), 7.26 (d, J=8.2 Hz, 2H), 7.11 (s, 1H), 3.25-3.20 (m, 6H), 3.17 (d, J=5.5 Hz, 4H), 2.65-2.59 (m, 1H), 2.44 (dd, J=2.7, 13.1 Hz, 1H), 2.37 (dd, J=7.0, 12.5 Hz, 1H), 2.19-2.04 (m, 1H), 1.98-1.89 (m, 1H), 1.85 (d, J=13.1 Hz, 1H), 1.74 (dd, J=3.7, 7.9 Hz, 2H), 1.71-1.60 (m, 3H), 1.56-1.45 (m, 8H), 1.44-1.37 (m, 4H), 1.36-1.25 (m, 2H), 1.16-1.09 (m, 2H), 1.05 (s, 3H), 1.04 (s, 3H), 1.00 (s, 3H), 0.95 (d, J=2.1 Hz, 1H), 0.91 (d, J=6.7 Hz, 3H), 0.81 (d, J=6.7 Hz, 3H), 0.78 (s, 3H), 0.72 (s, 3H).

Workup

  1. concentrationthe reaction mixture was concentrated to dryness
  2. dissolutionThe crude residue was dissolved in THF (1.2 mL)
  3. filtrationThe resulting solution was filtered
  4. custompurified

Sources & evidence

ORD record
ord-e06be4190b924f53a73e4b83bfec3ab5
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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