Sodium Carbonate Monohydrate → 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)cyclohex-3-enecarboxylate

HRID 1400994

Reaction equation

HRID 1400994 reaction equation
FC(F)(F)S(O[C:7]1[C:8]([CH3:36])([CH3:35])[C@H:9]2[C@:22]([CH3:25])([CH2:23][CH:24]=1)[C@@H:21]1[C@:12]([CH3:34])([C@@:13]3([CH3:33])[C@H:18]([CH2:19][CH2:20]1)[C@H:17]1[C@H:26]([C:29]([CH3:31])=[CH2:30])[CH2:27][CH2:28][C@:16]1([NH2:32])[CH2:15][CH2:14]3)[CH2:11][CH2:10]2)(=O)=O.CC1(C)C(C)(C)OB([C:47]2[CH2:52][CH2:51][CH:50]([C:53]([O:55][CH2:56][CH3:57])=[O:54])[CH2:49][CH:48]=2)O1.O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.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>[NH2:32][C@:16]12[CH2:28][CH2:27][C@@H:26]([C:29]([CH3:31])=[CH2:30])[C@@H:17]1[C@@H:18]1[C@@:13]([CH3:33])([CH2:14][CH2:15]2)[C@@:12]2([CH3:34])[C@@H:21]([C@:22]3([CH3:25])[C@@H:9]([CH2:10][CH2:11]2)[C:8]([CH3:35])([CH3:36])[C:7]([C:47]2[CH2:52][CH2:51][CH:50]([C:53]([O:55][CH2:56][CH3:57])=[O:54])[CH2:49][CH:48]=2)=[CH:24][CH2:23]3)[CH2:20][CH2:19]1

Participants

7

Reactant 3

HCID 2735133Sodium Carbonate MonohydrateHCID 592787964-(4,4,5,5-Tetramethyl-(1,3,2)dioxaborolan-2-yl)cyclohex-3-ene-1-carboxylic acid ethyl esterHCID 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 86692333ethyl 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)cyclohex-3-enecarboxylateYield 47.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To a sealable vial containing (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 (0.25 g, 0.448 mmol) was added ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-enecarboxylate (0.138 g, 0.493 mmol), sodium carbonate hydrate (0.167 g, 1.345 mmol), and palladium tetrakis (0.016 g, 0.013 mmol). The mixture was diluted with 1,4-dioxane (4 mL) and water (1 mL) then was flushed with nitrogen and was sealed and heated to 85° C. in an oil bath. After 5 h of heating, the mixture was cooled to rt, diluted with water (20 mL), and extracted with ethyl acetate (3×20 mL). The organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography using a 6-50% ethyl acetate in hexanes gradient and 40 g silica gel column. The fractions containing the expected product were combined and concentrated under reduced pressure to give ethyl 4-((1R,3 aS,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)cyclohex-3-enecarboxylate (0.119 g, 0.212 mmol, 47.3% yield) as an off-white solid. LCMS: m/e 562.6 (M+H)+, 2.13 min (method 1). 1H NMR (500 MHz, chloroform-d) δ=5.35 (br. s., 1H), 5.19 (d, J=6.1 Hz, 1H), 4.73 (d, J=1.9 Hz, 1H), 4.60 (s, 1H), 4.15 (q, J=7.1 Hz, 2H), 2.58-2.47 (m, 2H), 2.33-2.27 (m, 2H), 2.23-1.94 (m, 6H), 1.70 (s, 3H), 1.27 (t, 3H), 1.07 (s, 3H), 1.79-0.82 (m, 34H).

Workup

  1. customthen was flushed with nitrogen
  2. customwas sealed
  3. temperatureAfter 5 h of heating
  4. temperaturethe mixture was cooled to rt
  5. additiondiluted with water (20 mL)
  6. extractionextracted with ethyl acetate (3×20 mL)
  7. washThe organic layers were washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by flash chromatography
  12. additionThe fractions containing the expected product
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-598370ac54994e489ec5c96f13591937
Source dataset
uspto-grants-2014_12
Patent number
US08906889B2

Linked notes

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