Sodium Hydroxide → 2-fluoro-4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-(4-(methylsulfonyl)piperazin-1-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

HRID 85701Notes

Reaction equation

HRID 85701 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([C:12]2[C:13]([CH3:53])([CH3:52])[C@H:14]3[C@:27]([CH3:30])([CH2:28][CH:29]=2)[C@@H:26]2[C@:17]([CH3:51])([C@@:18]4([CH3:50])[C@H:23]([CH2:24][CH2:25]2)[C@H:22]2[C@H:31]([C:34]([CH3:36])=[CH2:35])[CH2:32][CH2:33][C@:21]2([NH:37][CH2:38][CH2:39][N:40]2[CH2:45][CH2:44][N:43]([S:46]([CH3:49])(=[O:48])=[O:47])[CH2:42][CH2:41]2)[CH2:20][CH2:19]4)[CH2:16][CH2:15]3)[CH:9]=[CH:8][C:3]=1[C:4]([O:6]C)=[O:5].[OH-].[Na+]>O1CCOCC1.CO>[F:1][C:2]1[CH:11]=[C:10]([C:12]2[C:13]([CH3:53])([CH3:52])[C@H:14]3[C@:27]([CH3:30])([CH2:28][CH:29]=2)[C@@H:26]2[C@:17]([CH3:51])([C@@:18]4([CH3:50])[C@H:23]([CH2:24][CH2:25]2)[C@H:22]2[C@H:31]([C:34]([CH3:36])=[CH2:35])[CH2:32][CH2:33][C@:21]2([NH:37][CH2:38][CH2:39][N:40]2[CH2:41][CH2:42][N:43]([S:46]([CH3:49])(=[O:48])=[O:47])[CH2:44][CH2:45]2)[CH2:20][CH2:19]4)[CH2:16][CH2:15]3)[CH:9]=[CH:8][C:3]=1[C:4]([OH:6])=[O:5]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86676630HCID 86676630, compound

Product 1

HCID 683581192-fluoro-4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-(4-(methylsulfonyl)piperazin-1-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 acidYield 52.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of methyl 2-fluoro-4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-(4-(methylsulfonyl)piperazin-1-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)benzoate (0.056 g, 0.074 mmol) in 1,4-dioxane (2 mL) was added NaOH (1N) (0.372 mL, 0.372 mmol). The mixture was heated to 60° C. for 6.5 h then was cooled to rt. The mixture was diluted with methanol and 1,4-dioxane, was filtered through a plug of glass wool and was purified by prep HPLC. The fractions containing the expected product were combined and were concentrated under reduced pressure to give 2-fluoro-4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-(4-(methylsulfonyl)piperazin-1-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 (30.1 mg, 0.039 mmol, 52.0% yield) as a white solid. LCMS: m/e 738.6 (M+H)+, 1.66 min (method 2). 1H NMR (400 MHz, Acetic acid d4) 67.92 (t, J=7.9 Hz, 1H), 7.04 (dd, J=8.0, 1.5 Hz, 1H), 7.01-6.96 (m, 1H), 5.38 (d, J=5.0 Hz, 1H), 4.81 (s, 1H), 4.70 (s, 1H), 3.59-3.25 (m, 8H), 3.15 (br. s., 4H), 2.90 (s, 3H), 2.94-2.81 (m, 1H), 1.72 (s, 3H), 1.21 (s, 3H), 1.09 (s, 3H), 1.04 (s, 3H), 0.99 (s, 3H), 0.97 (s, 3H), 2.23-0.83 (m, 22H).

Workup

  1. temperaturethen was cooled to rt
  2. filtrationwas filtered through a plug of glass wool
  3. customwas purified by prep HPLC
  4. additionThe fractions containing the expected product
  5. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-2f2e76de153349d999785ecf1e856141
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

Loading…