Phosphoric Acid → HCID 86731472, compound

HRID 1773025Notes

Reaction equation

HRID 1773025 reaction equation
[C:1]([O:7][CH3:8])(=[O:6])[CH2:2][CH2:3][CH:4]=[CH2:5].B1C2CCCC1CCC2.P(=O)(O)(O)O.[K].FC(F)(F)S(O[C:30]1[C:31]([CH3:59])([CH3:58])[C@H:32]2[C@:45]([CH3:48])([CH2:46][CH:47]=1)[C@@H:44]1[C@:35]([CH3:57])([C@@:36]3([CH3:56])[C@H:41]([CH2:42][CH2:43]1)[C@H:40]1[C@H:49]([C:52]([CH3:54])=[CH2:53])[CH2:50][CH2:51][C@:39]1([NH2:55])[CH2:38][CH2:37]3)[CH2:34][CH2:33]2)(=O)=O.C1(C)C=CC=CC=1>C1COCC1.O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:55][C@:39]12[CH2:51][CH2:50][C@@H:49]([C:52]([CH3:54])=[CH2:53])[C@@H:40]1[C@@H:41]1[C@@:36]([CH3:56])([CH2:37][CH2:38]2)[C@@:35]2([CH3:57])[C@@H:44]([C@:45]3([CH3:48])[C@@H:32]([CH2:33][CH2:34]2)[C:31]([CH3:58])([CH3:59])[C:30]([CH2:5][CH2:4][CH2:3][CH2:2][C:1]([O:7][CH3:8])=[O:6])=[CH:47][CH2:46]3)[CH2:43][CH2:42]1

Participants

11

Reactant 6

HCID 1004Phosphoric AcidHCID 1140TolueneHCID 789669-Borabicyclo(3.3.1)nonaneHCID 543664Methyl 4-pentenoateHCID 5462222PotassiumHCID 71698571(1R,3aS,5aR,5bR,7aR,11aR,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 trifluoromethanesulfonate

Product 1

HCID 86731472HCID 86731472, compoundYield 77%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of methyl 4-pentenoate (0.031 g, 0.269 mmol) in THF (1.5 mL) was cooled to 0° C. and 9-BBN (0.5M in THF) (0.574 mL, 0.287 mmol) was added dropwise. The mixture was removed from the ice bath and was stirred at rt for 2 h. To the solution was added a solution of phosphoric acid, potassium salt (1M) (0.448 mL, 0.448 mmol) followed by a solution of (1R,3aS,5aR,5bR,7aR,11aR,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 trifluoromethanesulfonate (0.1 g, 0.179 mmol) in 1,4-dioxane (1.5 mL) and finally 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride, Toluene (7.38 mg, 8.96 μmol). The mixture was heated to 85° C. for 16 h, cooled to rt, diluted with water (15 mL), and extracted with ethyl acetate (3×15 mL). The organic layers were combined, washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography using a 5-50% EtOAc in hexanes gradient and a 12 g silica gel column to give the title compound (0.072 g, 77% yield) as an off-white foam. LCMS: m/e: 524.5 (M+H)+, 2.04 min (method 1). 1H NMR (400 MHz, chloroform-d) δ=5.23 (d, J=5.3 Hz, 1H), 4.73 (d, J=2.0 Hz, 1H), 4.62-4.59 (m, 1H), 3.67 (s, 3H), 2.55 (td, J=10.9, 5.3 Hz, 1H), 2.33 (t, J=7.5 Hz, 2H), 2.09-1.92 (m, 4H), 1.70 (s, 3H), 1.07 (s, 3H), 0.97 (s, 6H), 0.89 (s, 3H), 0.83 (s, 3H), 1.78-0.80 (m, 26H).

Workup

  1. customThe mixture was removed from the ice bath
  2. temperatureThe mixture was heated to 85° C. for 16 h
  3. temperaturecooled to rt
  4. extractionextracted with ethyl acetate (3×15 mL)
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-f2e181b60947468ab0bf261eabf47b8f
Source dataset
uspto-grants-2016_02
Patent number
US09249180B2

Reaction notes

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