Phosphoric Acid → ethyl 4-(((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)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)methylene)cyclohexanecarboxylate

HRID 1773037Notes

Reaction equation

HRID 1773037 reaction equation
[NH2:1][C@:2]12[CH2:39][CH2:38][C@@H:37]([C:40]([CH3:42])=[CH2:41])[C@@H:3]1[C@@H:4]1[C@@:17]([CH3:20])([CH2:18][CH2:19]2)[C@@:16]2([CH3:21])[C@@H:7]([C@:8]3([CH3:36])[C@@H:13]([CH2:14][CH2:15]2)[C:12]([CH3:23])([CH3:22])[C:11]([CH:24]=[C:25]2[CH2:30][CH2:29][CH:28]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:27][CH2:26]2)=[CH:10][CH2:9]3)[CH2:6][CH2:5]1.P(=O)(O)(O)O.[K].[I-].[K+].Cl[CH2:52][CH2:53][N:54]1[CH2:59][CH2:58][S:57](=[O:61])(=[O:60])[CH2:56][CH2:55]1>C(#N)C>[O:60]=[S:57]1(=[O:61])[CH2:58][CH2:59][N:54]([CH2:53][CH2:52][NH:1][C@:2]23[CH2:39][CH2:38][C@@H:37]([C:40]([CH3:42])=[CH2:41])[C@@H:3]2[C@@H:4]2[C@@:17]([CH3:20])([CH2:18][CH2:19]3)[C@@:16]3([CH3:21])[C@@H:7]([C@:8]4([CH3:36])[C@@H:13]([CH2:14][CH2:15]3)[C:12]([CH3:22])([CH3:23])[C:11]([CH:24]=[C:25]3[CH2:30][CH2:29][CH:28]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:27][CH2:26]3)=[CH:10][CH2:9]4)[CH2:6][CH2:5]2)[CH2:55][CH2:56]1

Participants

7

Reactant 5

HCID 1004Phosphoric AcidHCID 4875Potassium IodideHCID 5462222PotassiumHCID 189487894-(2-chloroethyl)thiomorpholine1,1-dioxideHCID 86731496HCID 86731496, compound

Product 1

HCID 86731495ethyl 4-(((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)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)methylene)cyclohexanecarboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

To a sealable flask containing ethyl 4-(((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-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)methylene)cyclohexanecarboxylate (0.015 g, 0.026 mmol) was added phosphoric acid, potassium salt (0.028 g, 0.130 mmol), potassium iodide (0.013 g, 0.078 mmol) and 4-(2-chloroethyl)thiomorpholine 1,1-dioxide (0.015 g, 0.078 mmol). The mixture was diluted with acetonitrile (1 mL), flushed with nitrogen, sealed, and heated to 100° C. After heating the mixture for 22 h, it was cooled to rt, diluted with water (5 mL), and extracted with dichloromethane (3×5 mL). The organic layers were dried with sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was used in the next step with no additional purification. LCMS: m/e: 737.7 (M+H)1, 2.22 min (method 1).

Workup

  1. customflushed with nitrogen
  2. customsealed
  3. temperatureAfter heating the mixture for 22 h
  4. temperatureit was cooled to rt
  5. additiondiluted with water (5 mL)
  6. extractionextracted with dichloromethane (3×5 mL)
  7. dry with materialThe organic layers were dried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was used in the next step with no additional purification
  11. custom737.7 (M+H)1, 2.22 min (method 1)

Sources & evidence

ORD record
ord-e0ea9513bcd1460ca5778d143be87c28
Source dataset
uspto-grants-2016_02
Patent number
US09249180B2

Reaction notes

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