Dichloromethane → Isohexane ethyl acetate

HRID 2281560Notes

Reaction equation

HRID 2281560 reaction equation
B1C2CCCC1CCC2.[C:10]([O:14][C:15](=[O:36])[NH:16][C@H:17]([CH2:24][N:25]1[C:33](=[O:34])[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]1=[O:35])[CH2:18][C:19]([CH3:23])([CH3:22])[CH:20]=[CH2:21])([CH3:13])([CH3:12])[CH3:11].[O-]P([O-])([O-])=O.[K+].[K+].[K+].I[C:46]1[CH:60]=[CH:59][C:49]([O:50][CH2:51][C@@H:52]2[CH2:56][O:55][C:54]([CH3:58])([CH3:57])[O:53]2)=[CH:48][CH:47]=1.C(Cl)Cl>C1COCC1.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].CN(C=O)C>[CH3:51][CH2:52][O:53][C:54]([CH3:57])=[O:55].[CH3:24][CH2:17][CH2:18][CH:19]([CH3:22])[CH3:20].[C:10]([O:14][C:15](=[O:36])[NH:16][C@H:17]([CH2:24][N:25]1[C:26](=[O:35])[C:27]2[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:33]1=[O:34])[CH2:18][C:19]([CH3:22])([CH3:23])[CH2:20][CH2:21][C:46]1[CH:60]=[CH:59][C:49]([O:50][CH2:51][C@@H:52]2[CH2:56][O:55][C:54]([CH3:58])([CH3:57])[O:53]2)=[CH:48][CH:47]=1)([CH3:11])([CH3:12])[CH3:13]

Participants

10

Reactant 5

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 789669-Borabicyclo(3.3.1)nonaneHCID 67086996HCID 67086996, compoundHCID 67087070HCID 67087070, compound

Product 2

HCID 21882781Isohexane ethyl acetateHCID 67120695HCID 67120695, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

9-BBN (4.63 ml of a 0.5 M solution in THF, 0.23 mmol) is added to a solution of [(S)-1-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-3,3-dimethyl-pent-4-enyl]-carbamic acid tert-butyl ester (0.43 g, 0.116 mmol) in THF (15 ml) and the resulting colourless solution is stirred at room temperature overnight Anhydrous DMF (15 ml) is added to the solution, followed by 3 M aqueous K3PO4 solution (0.77 ml, 2.3 mmol), (R)-4-(4-Iodo-phenoxymethyl)-2,2-dimethyl-[1,3]dioxolane (267 mg, 0.28 mmol) and Pd(dppf)Cl2.DCM (47 mg, 0.058 mmol). The reaction is stirred at room temperature for 3 hours, 50° C. for 2 hours and then is allowed to cool to room temperature and filtered through a pad of Celite™ (filter material) which is washed with EtOAc (3×50 ml). The combined filtrates are washed with sat. aq. NaHCO3 solution (30 ml), dried (MgSO4) and the solvent removed in vacuo to afford a black oil. Multiple chromatography (SiO2, EtOAc/iso-hexane) yields [(S)-5-[4-((R)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenyl]-1-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-3,3-dimethyl-pentyl]-carbamic acid tert-butyl ester as a cream solid; [M+H-BOC]+ 481.

Workup

  1. additionis added to the solution
  2. temperatureto cool to room temperature
  3. filtrationfiltered through a pad of Celite™ (filter material) which
  4. washis washed with EtOAc (3×50 ml)
  5. washThe combined filtrates are washed with sat. aq. NaHCO3 solution (30 ml)
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed in vacuo
  8. customto afford a black oil

Sources & evidence

ORD record
ord-f4717b67443540b3b8469f533008b9fd
Source dataset
uspto-grants-2015_09
Patent number
US09139586B2

Reaction notes

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