Lithium Chloride → HCID 67776421, compound

HRID 406886Notes

Reaction equation

C([Sn](CCCC)(CCCC)[C:6]1[CH:10]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:8][N:7]=1)CCC.[C:24]([O:32][CH2:33][C@:34]12[CH2:67][CH2:66][C@@H:65]([C:68]([CH3:70])=[CH2:69])[C@@H:35]1[C@@H:36]1[C@@:49]([CH3:52])([CH2:50][CH2:51]2)[C@@:48]2([CH3:53])[C@@H:39]([C@:40]3([CH3:64])[C@@H:45]([CH2:46][CH2:47]2)[C:44]([CH3:55])([CH3:54])[C:43](OS(C(F)(F)F)(=O)=O)=[CH:42][CH2:41]3)[CH2:38][CH2:37]1)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[Cl-].[Li+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:24]([O:32][CH2:33][C@:34]12[CH2:67][CH2:66][C@@H:65]([C:68]([CH3:70])=[CH2:69])[C@@H:35]1[C@@H:36]1[C@@:49]([CH3:52])([CH2:50][CH2:51]2)[C@@:48]2([CH3:53])[C@@H:39]([C@:40]3([CH3:64])[C@@H:45]([CH2:46][CH2:47]2)[C:44]([CH3:54])([CH3:55])[C:43]([C:6]2[CH:10]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:8][N:7]=2)=[CH:42][CH2:41]3)[CH2:38][CH2:37]1)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

Conditions

Temperature: 85 °C

Procedure

To a sealable vial containing ethyl 3-(tributylstannyl)-1H-pyrazole-5-carboxylate (0.052 g, 0.122 mmol) was added ((1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-9-(trifluoromethylsulfonyloxy)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-3a-yl)methyl benzoate (0.075 g, 0.111 mmol), lithium chloride (0.014 g, 0.332 mmol), and tetrakis(triphenylphosphine)palladium(0) (6.40 mg, 5.54 μmol). The mixture was diluted with 1,4-Dioxane (2 mL) and was flushed with N2. The vial was sealed and heated to 85° C. for 15.5 h. The mixture was cooled to rt, was diluted with water (4 mL) and was extracted with dichloromethane (3×4 mL). The combined organic layers were dried with Na2SO4. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue purified by Biotage flash chromatography using a 0-25% EtOAc in hexanes gradient. The fractions containing the expected product were combined and concentrated under reduced pressure to give ethyl 3-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(benzoyloxymethyl)-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)-1H-pyrazole-5-carboxylate (0.070 g, 0.105 mmol, 95% yield) as a white solid. LCMS: m/e 665.66 (M−H)−, 2.74 min (method 1). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 0.85-1.84 (m, 21H), 0.91 (s, 3H), 1.02 (s, 3H), 1.03 (br. s., 3H), 1.05 (s, 3H), 1.10 (s, 3H), 1.71 (s, 3H), 1.89-2.07 (m, 3H), 2.15 (dd, J=17.70, 6.41 Hz, 1H), 2.53 (td, J=11.06, 5.95 Hz, 1H), 4.11 (d, J=10.99 Hz, 1H), 4.38 (q, J=7.02 Hz, 2H), 4.52 (d, J=10.07 Hz, 1H), 4.61 (s, 1H), 4.72 (d, J=1.53 Hz, 1H), 5.75 (d, J=4.58 Hz, 1H), 6.73 (s, 1H), 7.44 (t, J=7.78 Hz, 2H), 7.55 (t, J=7.32 Hz, 1H), 8.05 (d, J=7.02 Hz, 2H).

Workup

customwas flushed with N2
customThe vial was sealed
temperatureThe mixture was cooled to rt
additionwas diluted with water (4 mL)
extractionwas extracted with dichloromethane (3×4 mL)
dry with materialThe combined organic layers were dried with Na2SO4
customThe drying agent was removed by filtration
concentrationthe filtrate was concentrated under reduced pressure
customThe residue purified by Biotage flash chromatography
additionThe fractions containing the expected product
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-24099fbca98648dfad82dd88f1a8beb1
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754068B2

Reaction notes

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