Hydrochloric Acid → 3-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13 aR,13bR)-3a-((2-((1R,4R)-2,2-dioxido-2-thia-5-azabicyclo[2.2.1]heptan-5-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)bicyclo[3.1.0]hex-2-ene-6-carboxylic acid

HRID 338655Notes

Reaction equation

HRID 338655 reaction equation
[O:1]=[S:2]1(=[O:52])[CH2:7][CH:6]2[CH2:8][C@H:3]1[CH2:4][N:5]2[CH2:9][CH2:10][NH:11][C@:12]12[CH2:48][CH2:47][C@@H:46]([C:49]([CH3:51])=[CH2:50])[C@@H:13]1[C@@H:14]1[C@@:27]([CH3:30])([CH2:28][CH2:29]2)[C@@:26]2([CH3:31])[C@@H:17]([C@:18]3([CH3:45])[C@@H:23]([CH2:24][CH2:25]2)[C:22]([CH3:33])([CH3:32])[C:21]([C:34]2[CH2:39][CH:38]4[CH:36]([CH:37]4[C:40]([O:42]CC)=[O:41])[CH:35]=2)=[CH:20][CH2:19]3)[CH2:16][CH2:15]1.[OH-].[Na+].Cl.O>O1CCOCC1>[O:52]=[S:2]1(=[O:1])[CH2:7][C@H:6]2[CH2:8][C@@H:3]1[CH2:4][N:5]2[CH2:9][CH2:10][NH:11][C@:12]12[CH2:48][CH2:47][C@@H:46]([C:49]([CH3:51])=[CH2:50])[C@@H:13]1[C@@H:14]1[C@@:27]([CH3:30])([CH2:28][CH2:29]2)[C@@:26]2([CH3:31])[C@@H:17]([C@:18]3([CH3:45])[C@@H:23]([CH2:24][CH2:25]2)[C:22]([CH3:32])([CH3:33])[C:21]([C:34]2[CH2:39][CH:38]4[CH:36]([CH:37]4[C:40]([OH:42])=[O:41])[CH:35]=2)=[CH:20][CH2:19]3)[CH2:16][CH2:15]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 89886506ethyl 3-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-((1S)-2,2-dioxido-2-thia-5-azabicyclo[2.2.1]heptan-5-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)bicyclo[3.1.0]hex-2-ene-6-carboxylate

Product 1

HCID 722013303-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13 aR,13bR)-3a-((2-((1R,4R)-2,2-dioxido-2-thia-5-azabicyclo[2.2.1]heptan-5-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)bicyclo[3.1.0]hex-2-ene-6-carboxylic acid

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of ethyl 3-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-((1S)2,2-dioxido-2-thia-5-azabicyclo[2.2.1]heptan-5-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)bicyclo[3.1.0]hex-2-ene-6-carboxylate (28 mg, 0.03 mmol) in 1,4-dioxane (2 mL) was added sodium hydroxide (1N) (0.149 mL, 0.149 mmol). The mixture was warmed to 70° C. After heating the mixture for 16 h, it was cooled to rt and was acidified by adding 1 mL of 1N HCl. Then water was added until solids formed. The solids were collected by filtration, dissolved in 1,4-dioxane and methanol and purified by prep HPLC (method 12) to afford 3-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13 aR,13bR)-3a-((2-((1R,4R)-2,2-dioxido-2-thia-5-azabicyclo[2.2.1]heptan-5-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)bicyclo[3.1.0]hex-2-ene-6-carboxylic acid as two different isomers (isomer 1, 16.5% and isomer 2, 11.5%)

Workup

  1. temperatureAfter heating the mixture for 16 h
  2. temperatureit was cooled to rt
  3. customformed
  4. filtrationThe solids were collected by filtration
  5. dissolutiondissolved in 1,4-dioxane
  6. custommethanol and purified by prep HPLC (method 12)

Sources & evidence

ORD record
ord-558a6cef301248eaa37303b51fa1fbda
Source dataset
uspto-grants-2014_11
Patent number
US08889854B2

Reaction notes

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