Triethylamine → diisopropyl 6-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(((tert-butyldimethylsilyl)oxy)carbonyl)-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

HRID 1400978Notes

Reaction equation

C([O:8][C:9]([C@:11]12[CH2:55][CH2:54][C@@H:53]([C:56]([CH3:58])=[CH2:57])[C@@H:12]1[C@@H:13]1[C@@:26]([CH3:29])([CH2:27][CH2:28]2)[C@@:25]2([CH3:30])[C@@H:16]([C@:17]3([CH3:52])[C@@H:22]([CH2:23][CH2:24]2)[C:21]([CH3:32])([CH3:31])[C:20]([C:33]2[CH2:51][C:35]4([CH2:38][C:37]([C:45]([O:47][CH:48]([CH3:50])[CH3:49])=[O:46])([C:39]([O:41][CH:42]([CH3:44])[CH3:43])=[O:40])[CH2:36]4)[CH:34]=2)=[CH:19][CH2:18]3)[CH2:15][CH2:14]1)=[O:10])C1C=CC=CC=1.C(N(CC)CC)C.[C:66]([SiH:70]([CH3:72])[CH3:71])([CH3:69])([CH3:68])[CH3:67]>ClCCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Si:70]([O:10][C:9]([C@:11]12[CH2:55][CH2:54][C@@H:53]([C:56]([CH3:58])=[CH2:57])[C@@H:12]1[C@@H:13]1[C@@:26]([CH3:29])([CH2:27][CH2:28]2)[C@@:25]2([CH3:30])[C@@H:16]([C@:17]3([CH3:52])[C@@H:22]([CH2:23][CH2:24]2)[C:21]([CH3:31])([CH3:32])[C:20]([C:33]2[CH2:51][C:35]4([CH2:36][C:37]([C:39]([O:41][CH:42]([CH3:43])[CH3:44])=[O:40])([C:45]([O:47][CH:48]([CH3:50])[CH3:49])=[O:46])[CH2:38]4)[CH:34]=2)=[CH:19][CH2:18]3)[CH2:15][CH2:14]1)=[O:8])([C:66]([CH3:69])([CH3:68])[CH3:67])([CH3:72])[CH3:71]

Participants

Conditions

Temperature: 60 °C

Procedure

To a rbf containing a solution of diisopropyl 6-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((benzyloxy)carbonyl)-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 (0.053 g, 0.047 mmol (based on 70% purity)) in DCE (2 mL) was added triethylamine (10.43 μl, 0.075 mmol), t-butyldimethylsilane (0.016 mL, 0.094 mmol), and palladium(II) acetate (2.63 mg, 0.012 mmol). The mixture was flushed with nitrogen, then was heated to 60° C. for 4.5 h. An additional 3 mg of palladium (II) acetate were added along with 16 μL of t-butyldimethylsilane. The mixture was flushed with nitrogen, then was heated to 60° C. for an additional 2.5 h. The mixture was cooled to rt and was filtered through a plug of celite and sicla gel which was then washed with 25% EtOAc in hexanes. The filtrate was concentrated under reduced pressure to give diisopropyl 6-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13 aR,13bR)-3a-(((tert-butyldimethylsilyl)oxy)carbonyl)-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 (0.026 g, 0.021 mmol (based on 65% purity), 44.2% yield) as a clear, colorless foam. 1H NMR (500 MHz, chloroform-d) δ=5.86 (s, 1H), 5.51 (dd, J=6.3, 1.7 Hz, 1H), 5.13-5.01 (m, 2H), 4.73 (s, 1H), 4.60 (s, 1H), 3.06 (td, J=10.8, 4.1 Hz, 1H), 2.73-2.66 (m, 4H), 2.62-2.55 (m, 2H), 1.69 (s, 3H), 0.96 (s, 9H), 2.54-0.76 (m, 49H), 0.30-0.28 (m, 6H). The material was used in the next step with no additional purification.

Workup

customThe mixture was flushed with nitrogen
additionAn additional 3 mg of palladium (II) acetate were added along with 16 μL of t-butyldimethylsilane
customThe mixture was flushed with nitrogen
temperaturewas heated to 60° C. for an additional 2.5 h
temperatureThe mixture was cooled to rt
filtrationwas filtered through a plug of celite
washsicla gel which was then washed with 25% EtOAc in hexanes
concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record: ord-93cf9af9039f4206a47f1953cd6476b4
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08906889B2

Reaction notes

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