Boron trifluoride etherate → diisopropyl 6-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-morpholinoethyl)amino)-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)spiro[3.3]hept-5-ene-2,2-dicarboxylate

HRID 1401007Notes

Reaction equation

HRID 1401007 reaction equation
Cl[CH2:2][CH2:3][NH:4][C@:5]12[CH2:49][CH2:48][C@@H:47]([C:50]([CH3:52])=[CH2:51])[C@@H:6]1[C@@H:7]1[C@@:20]([CH3:23])([CH2:21][CH2:22]2)[C@@:19]2([CH3:24])[C@@H:10]([C@:11]3([CH3:46])[C@@H:16]([CH2:17][CH2:18]2)[C:15]([CH3:26])([CH3:25])[C:14]([C:27]2[CH2:45][C:29]4([CH2:32][C:31]([C:39]([O:41][CH:42]([CH3:44])[CH3:43])=[O:40])([C:33]([O:35][CH:36]([CH3:38])[CH3:37])=[O:34])[CH2:30]4)[CH:28]=2)=[CH:13][CH2:12]3)[CH2:9][CH2:8]1.B(F)(F)F.CCOCC.[NH:62]1[CH2:67][CH2:66][O:65][CH2:64][CH2:63]1>C1C=CC=CC=1.[Cl-].[NH4+].Cl>[CH3:23][C@:20]12[C@@:19]3([CH3:24])[C@@H:10]([C@:11]4([CH3:46])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:26])([CH3:25])[C:14]([C:27]3[CH2:45][C:29]5([CH2:30][C:31]([C:33]([O:35][CH:36]([CH3:38])[CH3:37])=[O:34])([C:39]([O:41][CH:42]([CH3:44])[CH3:43])=[O:40])[CH2:32]5)[CH:28]=3)=[CH:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:47]([C:50]([CH3:52])=[CH2:51])[CH2:48][CH2:49][C@:5]1([NH:4][CH2:3][CH2:2][N:62]1[CH2:67][CH2:66][O:65][CH2:64][CH2:63]1)[CH2:22][CH2:21]2

Participants

7

Reactant 3

HCID 8000Boron trifluoride etherateHCID 8083MorpholineHCID 86692358HCID 86692358, compound

Product 1

HCID 86692359diisopropyl 6-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-morpholinoethyl)amino)-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)spiro[3.3]hept-5-ene-2,2-dicarboxylateYield 42.9%

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 313Hydrochloric AcidSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of diisopropyl 6-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-chloroethyl)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)spiro[3.3]hept-5-ene-2,2-dicarboxylate (18 mg, 0.024 mmol) in a solution of borontrifluoride etherate in benzene (BF3.Et2O 2% by volume, 2 mL) at RT, was added morpholine (75 μl, 0.857 mmol) forming a cloudy mixture. The mixture was kept at 80° C. for 2 hours. The reaction was diluted with a saturated solution of ammonium chloride in 0.5 N HCl, organic materials were extracted into ethyl acetate (25 mL) three times. The organic extracts were combined and washed with a solution of sodium bicarbonate, the organic materials were concentrated, and purified by silica gel chromatography eluted with mixture of ethyl acetate and hexanes to give 8.1 mg (40%) of the desired product. MS: m/e 787.6 (M+H)+. 1H NMR (400 MHz, CHLOROFORM-d) δ 5.87 (s, 1H), 5.55-5.49 (m, 1H), 5.15-5.00 (m, 2H), 4.72 (br. s., 1H), 4.59 (br. s., 1H), 3.73 (t, J=4.4 Hz, 4H), 2.70 (s, 4H), 2.59 (d, J=2.3 Hz, 3H), 2.56-2.34 (m, 6H), 2.10 (dd, J=17.9, 6.7 Hz, 1H), 1.92-1.72 (m, 4H), 1.70 (s, 4H), 1.67-1.28 (m, 14H), 1.25 (dd, J=6.3, 5.0 Hz, 14H), 1.15 (m, 5H), 1.10 (m, 5H), 1.07 (m, 5H), 0.97 (s, 3H), 0.82 (s, 3H).

Workup

  1. customforming a cloudy mixture
  2. extractionwere extracted into ethyl acetate (25 mL) three times
  3. washwashed with a solution of sodium bicarbonate
  4. concentrationthe organic materials were concentrated
  5. custompurified by silica gel chromatography
  6. washeluted with mixture of ethyl acetate and hexanes

Sources & evidence

ORD record
ord-c440a9b279654fca82bab17168a4c7e8
Source dataset
uspto-grants-2014_12
Patent number
US08906889B2

Reaction notes

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