Dichloromethane → HCID 86731489, compound

HRID 1773030Notes

Reaction equation

HRID 1773030 reaction equation
[C:1]([O:6][CH3:7])(=[O:5])[CH2:2][CH:3]=[CH2:4].B1C2CCCC1CCC2.[O-]P([O-])([O-])=O.[K+].[K+].[K+].FC(F)(F)S(O[C:31]1[C:32]([CH3:70])([CH3:69])[C@H:33]2[C@:46]([CH3:49])([CH2:47][CH:48]=1)[C@@H:45]1[C@:36]([CH3:68])([C@@:37]3([CH3:67])[C@H:42]([CH2:43][CH2:44]1)[C@H:41]1[C@H:50]([C:53]([CH3:55])=[CH2:54])[CH2:51][CH2:52][C@:40]1([NH:56][CH2:57][CH2:58][N:59]1[CH2:64][CH2:63][S:62](=[O:66])(=[O:65])[CH2:61][CH2:60]1)[CH2:39][CH2:38]3)[CH2:35][CH2:34]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:66]=[S:62]1(=[O:65])[CH2:63][CH2:64][N:59]([CH2:58][CH2:57][NH:56][C@:40]23[CH2:52][CH2:51][C@@H:50]([C:53]([CH3:55])=[CH2:54])[C@@H:41]2[C@@H:42]2[C@@:37]([CH3:67])([CH2:38][CH2:39]3)[C@@:36]3([CH3:68])[C@@H:45]([C@:46]4([CH3:49])[C@@H:33]([CH2:34][CH2:35]3)[C:32]([CH3:69])([CH3:70])[C:31]([CH2:4][CH2:3][CH2:2][C:1]([O:6][CH3:7])=[O:5])=[CH:48][CH2:47]4)[CH2:44][CH2:43]2)[CH2:60][CH2:61]1

Participants

10

Reactant 5

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 77314Methyl 3-butenoateHCID 789669-Borabicyclo(3.3.1)nonaneHCID 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 86731489HCID 86731489, compoundYield 71.2%

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 but-3-enoate (16.7 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) (59.0 mg, 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 4-((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)butanoate (53 mg, 0.079 mmol, 71% yield). LC/MS: m/e 671.5 (M+H)+, 2.36 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-b5114d19a16647bfa10c2f01b0383cfe
Source dataset
uspto-grants-2016_02
Patent number
US09249180B2

Reaction notes

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