Dichloromethane → HCID 86731488, compound

HRID 1773029Notes

Reaction equation

HRID 1773029 reaction equation
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][CH2:3][CH2:4][CH:5]=[CH2:6].B1C2CCCC1CCC2.[O-]P([O-])([O-])=O.[K+].[K+].[K+].FC(F)(F)S(O[C:33]1[C:34]([CH3:72])([CH3:71])[C@H:35]2[C@:48]([CH3:51])([CH2:49][CH:50]=1)[C@@H:47]1[C@:38]([CH3:70])([C@@:39]3([CH3:69])[C@H:44]([CH2:45][CH2:46]1)[C@H:43]1[C@H:52]([C:55]([CH3:57])=[CH2:56])[CH2:53][CH2:54][C@:42]1([NH:58][CH2:59][CH2:60][N:61]1[CH2:66][CH2:65][S:64](=[O:68])(=[O:67])[CH2:63][CH2:62]1)[CH2:41][CH2:40]3)[CH2:37][CH2:36]2)(=O)=O.C(Cl)Cl>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]>[O:68]=[S:64]1(=[O:67])[CH2:65][CH2:66][N:61]([CH2:60][CH2:59][NH:58][C@:42]23[CH2:54][CH2:53][C@@H:52]([C:55]([CH3:57])=[CH2:56])[C@@H:43]2[C@@H:44]2[C@@:39]([CH3:69])([CH2:40][CH2:41]3)[C@@:38]3([CH3:70])[C@@H:47]([C@:48]4([CH3:51])[C@@H:35]([CH2:36][CH2:37]3)[C:34]([CH3:71])([CH3:72])[C:33]([CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][C:1]([O:8][CH3:9])=[O:7])=[CH:50][CH2:49]4)[CH2:46][CH2:45]2)[CH2:62][CH2:63]1

Participants

10

Reactant 5

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 789669-Borabicyclo(3.3.1)nonaneHCID 520082Methyl 5-HexenoateHCID 71698666(1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)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 86731488HCID 86731488, compoundYield 62.1%

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 hex-5-enoate (21.4 mg, 0.167 mmol) in THF (3 mL) under argon was cooled to 0° C. and 9-BBN (0.5 M in THF) (0.356 mL, 0.178 mmol) was added dropwise. The reaction mixture was warmed to rt and was stirred for 2 h. A solution of potassium phosphate tribasic (1M) (0.278 mL, 0.278 mmol) was added to the reaction mixture followed by a solution of (1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)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 (80 mg, 0.111 mmol) in dioxane (3.00 mL). PdCl2(dppf).CH2Cl2 adduct (4.5 mg, 5.6 μmol) was then added and the reaction mixture was stirred for 16 h at 85° C. The reaction mixture was cooled to room temperature and was diluted with water (10 mL). The aqueous layer was extracted with ethyl acetate (3×10 mL). The combined organic layers were dried (sodium sulfate) and concentrated under vacuum. The product was purified by column chromatography on silica gel (0%>50% ethyl acetate in hexanes) to afford methyl 6-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)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)hexanoate (48.2 mg, 62% yield). LC/MS: m/e 699.5 (M+H)+, 2.45 min (method 3).

Workup

  1. stirringthe reaction mixture was stirred for 16 h at 85° C
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×10 mL)
  4. dry with materialThe combined organic layers were dried (sodium sulfate)
  5. concentrationconcentrated under vacuum
  6. customThe product was purified by column chromatography on silica gel (0%>50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-1bfbad9f5e5a46ccbf5e71f8479d7bd5
Source dataset
uspto-grants-2016_02
Patent number
US09249180B2

Reaction notes

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