Phosphoric Acid → HCID 86676623, compound

HRID 85699Notes

Reaction equation

HRID 85699 reaction equation
Cl.[NH2:2][C@:3]12[CH2:39][CH2:38][C@@H:37]([C:40]([CH3:42])=[CH2:41])[C@@H:4]1[C@@H:5]1[C@@:18]([CH3:21])([CH2:19][CH2:20]2)[C@@:17]2([CH3:22])[C@@H:8]([C@:9]3([CH3:36])[C@@H:14]([CH2:15][CH2:16]2)[C:13]([CH3:24])([CH3:23])[C:12]([C:25]2[CH:34]=[CH:33][C:28]([C:29]([O:31][CH3:32])=[O:30])=[C:27]([F:35])[CH:26]=2)=[CH:11][CH2:10]3)[CH2:7][CH2:6]1.Cl.Cl[CH2:45][CH2:46][N:47]1[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1.P(=O)(O)(O)O.[K].[I-].[K+]>C(#N)C>[F:35][C:27]1[CH:26]=[C:25]([C:12]2[C:13]([CH3:23])([CH3:24])[C@H:14]3[C@:9]([CH3:36])([CH2:10][CH:11]=2)[C@@H:8]2[C@:17]([CH3:22])([C@@:18]4([CH3:21])[C@H:5]([CH2:6][CH2:7]2)[C@H:4]2[C@H:37]([C:40]([CH3:42])=[CH2:41])[CH2:38][CH2:39][C@:3]2([NH:2][CH2:45][CH2:46][N:47]2[CH2:52][CH2:51][O:50][CH2:49][CH2:48]2)[CH2:20][CH2:19]4)[CH2:16][CH2:15]3)[CH:34]=[CH:33][C:28]=1[C:29]([O:31][CH3:32])=[O:30]

Participants

7

Reactant 5

HCID 1004Phosphoric AcidHCID 4875Potassium IodideHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 5462222PotassiumHCID 86676627HCID 86676627, compound

Product 1

HCID 86676623HCID 86676623, compoundYield 68.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

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 hydrochloride (0.1 g, 0.167 mmol) was added 4-(2-chloroethyl)morpholine hydrochloride (0.093 g, 0.501 mmol), phosphoric acid, potassium salt (0.156 g, 0.735 mmol) and potassium iodide (0.075 g, 0.451 mmol). The mixture was diluted with acetonitrile (3 mL), was flushed with nitrogen, then the vial was sealed and heated to 120° C. After heating the mixture for 16 h, the mixture was cooled to rt. The crude product was adsorbed to silica gel then was purified by flash chromatography using a Thomson 12 g silica gel column and a 0-5% methanol in dichloromethane gradient. The fractions containing the expected product were combined and 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-morpholinoethylamino)-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 (77 mg, 0.114 mmol, 68.3% yield) as an off-white foam. LCMS: m/e 675.5 (M+H)+, 1.91 min (method 2).

Workup

  1. customwas flushed with nitrogen
  2. customthe vial was sealed
  3. temperatureAfter heating the mixture for 16 h
  4. temperaturethe mixture was cooled to rt
  5. customthen was purified by flash chromatography
  6. additionThe fractions containing the expected product
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cb838f3440bb4f79b31cb38569274815
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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