Phosphoric Acid → HCID 86676624, compound

HRID 85694Notes

Reaction equation

HRID 85694 reaction equation
[NH2:1][C@:2]12[CH2:38][CH2:37][C@@H:36]([C:39]([CH3:41])=[CH2:40])[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([CH3:35])[C@@H:13]([CH2:14][CH2:15]2)[C:12]([CH3:23])([CH3:22])[C:11]([C:24]2[CH:33]=[CH:32][C:27]([C:28]([O:30][CH3:31])=[O:29])=[C:26]([F:34])[CH:25]=2)=[CH:10][CH2:9]3)[CH2:6][CH2:5]1.[I-].[K+].P(=O)(O)(O)O.[K].[C:50](#[N:52])[CH3:51]>>[F:34][C:26]1[CH:25]=[C:24]([C:11]2[C:12]([CH3:22])([CH3:23])[C@H:13]3[C@:8]([CH3:35])([CH2:9][CH:10]=2)[C@@H:7]2[C@:16]([CH3:21])([C@@:17]4([CH3:20])[C@H:4]([CH2:5][CH2:6]2)[C@H:3]2[C@H:36]([C:39]([CH3:41])=[CH2:40])[CH2:37][CH2:38][C@:2]2([NH:1][CH2:51][CH2:50][N:52]2[CH2:25][CH2:26][CH2:27][C:28]2=[O:29])[CH2:19][CH2:18]4)[CH2:15][CH2:14]3)[CH:33]=[CH:32][C:27]=1[C:28]([O:30][CH3:31])=[O:29]

Participants

6

Reactant 5

HCID 1004Phosphoric AcidHCID 4875Potassium IodideHCID 6342AcetonitrileHCID 5462222PotassiumHCID 68358156methyl 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)-2-fluorobenzoate

Product 1

HCID 86676624HCID 86676624, compoundYield 41.7%

Conditions

Temperature
120 °C

Procedure

To a sealable flask containing methyl 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)-2-fluorobenzoate (50 mg, 0.089 mmol) was added potassium iodide (39.9 mg, 0.240 mmol) and phosphoric acid, potassium salt (83 mg, 0.392 mmol). The mixture was diluted with acetonitrile (1 mL) and the crude alkylating solution described above (1.007 mL, 0.445 mmol) was added. The mixture was flushed with N2 and the vial was sealed and heated to 120° C. After 15.5 h of heating, the mixture was cooled to rt. An additional 0.5 mL of the crude alkylating solution was added and the mixture was again heated to 120° C. After 70.25 h, the mixture was cooled to rt. The mixture was adsorbed to silica gel and was purified by flash chromatography using a 0-5% MeOH in DCM gradient and a Thomson 12 g silica gel column. The fractions containing the expected product were combined and were concentrated under reduced pressure to give methyl 2-fluoro-4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-(2-(2-oxopyrrolidin-1-yl)ethylamino)-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 (25 mg, 0.037 mmol, 41.7% yield) as a yellow film. LCMS: m/e 673.5 (M+H)+, 2.03 min (method 2).

Workup

  1. additionwas added
  2. customThe mixture was flushed with N2
  3. customthe vial was sealed
  4. temperatureAfter 15.5 h of heating
  5. temperaturethe mixture was cooled to rt
  6. additionAn additional 0.5 mL of the crude alkylating solution was added
  7. temperaturethe mixture was again heated to 120° C
  8. temperaturethe mixture was cooled to rt
  9. customwas purified by flash chromatography
  10. additionThe fractions containing the expected product
  11. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-21c3ebf7c0da4bff9e71ba08b38c8d5a
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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