Sodium Hydroxide → HCID 86676613, compound

HRID 85669Notes

Reaction equation

HRID 85669 reaction equation
[F:1][CH2:2][CH2:3][NH:4][C@:5]12[CH2:40][CH2:39][C@@H:38]([C:41]([CH3:43])=[CH2:42])[C@@H:6]1[C@@H:7]1[C@@:20]([CH3:23])([CH2:21][CH2:22]2)[C@@:19]2([CH3:24])[C@@H:10]([C@:11]3([CH3:37])[C@@H:16]([CH2:17][CH2:18]2)[C:15]([CH3:26])([CH3:25])[C:14]([C:27]2[CH:36]=[CH:35][C:30]([C:31]([O:33]C)=[O:32])=[CH:29][CH:28]=2)=[CH:13][CH2:12]3)[CH2:9][CH2:8]1.[OH-].[Na+]>O1CCOCC1.CO>[F:1][CH2:2][CH2:3][NH:4][C@:5]12[CH2:40][CH2:39][C@@H:38]([C:41]([CH3:43])=[CH2:42])[C@@H:6]1[C@@H:7]1[C@@:20]([CH3:23])([CH2:21][CH2:22]2)[C@@:19]2([CH3:24])[C@@H:10]([C@:11]3([CH3:37])[C@@H:16]([CH2:17][CH2:18]2)[C:15]([CH3:26])([CH3:25])[C:14]([C:27]2[CH:28]=[CH:29][C:30]([C:31]([OH:33])=[O:32])=[CH:35][CH:36]=2)=[CH:13][CH2:12]3)[CH2:9][CH2:8]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86676612HCID 86676612, compound

Product 1

HCID 86676613HCID 86676613, compoundYield 48.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
85 °C

Procedure

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-fluoroethyl)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)benzoate (0.059 g, 0.100 mmol) in 1,4-dioxane (2 mL) was added NaOH (1N) (0.5 mL, 0.500 mmol). The mixture was heated to 85° C. for 15.25 h, was cooled to rt, then was diluted with methanol and 1,4-dioxane and was purified by prep HPLC. The fractions containing the expected product were combined and concentrated under reduced pressure to give 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-fluoroethyl)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 (29.2 mg, 0.048 mmol, 48.2% yield) as a white solid. LCMS: m/e 576.6 (M+H)+, 1.74 min (method 2). 1H NMR (400 MHz, Acetic acid d4) δ 7.99 (d, J=8.53 Hz, 2H), 7.26 (d, J=8.28 Hz, 2H), 5.33 (d, J=4.77 Hz, 1H), 4.73-4.99 (m, 3H), 4.70 (s, 1H), 3.41-3.73 (m, 2H), 2.83-2.94 (m, 1H), 1.73 (s, 3H), 1.19 (s, 3H), 1.11 (s, 3H), 1.05 (s, 3H), 0.98 (s, 3H), 0.96 (s, 3H), 0.82-2.27 (m, 22H).

Workup

  1. temperaturewas cooled to rt
  2. customwas purified by prep HPLC
  3. additionThe fractions containing the expected product
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cb51307118d04d298a91510281612cc1
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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