Diethyl Ether → HCID 71136852, compound

HRID 1468873Notes

Reaction equation

HRID 1468873 reaction equation
[Cl-].[C:2]([O:6][C:7](=[O:10])[CH2:8][Zn+])([CH3:5])([CH3:4])[CH3:3].CCOCC.Br[C:17]1[CH:42]=[CH:41][C:20]([CH2:21][O:22][CH2:23][C@@H:24]2[CH2:26][C@@H:25]2[CH:27]2[CH2:32][CH2:31][N:30]([C:33]3[O:37][N:36]=[C:35]([CH:38]([CH3:40])[CH3:39])[N:34]=3)[CH2:29][CH2:28]2)=[C:19]([F:43])[CH:18]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:43][C:19]1[CH:18]=[C:17]([CH2:8][C:7]([O:6][C:2]([CH3:5])([CH3:4])[CH3:3])=[O:10])[CH:42]=[CH:41][C:20]=1[CH2:21][O:22][CH2:23][C@@H:24]1[CH2:26][C@@H:25]1[CH:27]1[CH2:32][CH2:31][N:30]([C:33]2[O:37][N:36]=[C:35]([CH:38]([CH3:40])[CH3:39])[N:34]=2)[CH2:29][CH2:28]1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 71116042HCID 71116042, compoundHCID 178451183HCID 178451183, compound

Product 1

HCID 71136852HCID 71136852, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

A 0.5 M solution of 2-(tert-butyloxy)-2-oxoethylzinc chloride in Et2O (14.6 mL, 7.3 mmol) was added to a mixture of 5-(4-((1R,2R)-2-((4-bromo-2-fluorobenzyloxy)methyl)cyclopropyl)piperidin-1-yl)-3-isopropyl-1,2,4-oxadiazole (Step B product, 1.1 g, 2.43 mmol), Pd2(dba)3 (110 mg, 0.122 mmol), and X-PHOS (116 mg, 0.243 mmol) in anhydrous THF (3 mL). The reaction mixture was stirred and heated at 65° C. overnight. The following morning the mixture was cooled to rt and filtered through a plug of celite, washing with EtOAc. The volatiles were removed under reduced pressure and the residue was loaded onto a silica column (KP-Sil 50 g SNAP column, Biotage system) eluting with a range of 5-45% EtOAc/Hex over 13 CV to give the desired compound (910 mg, 78%). LC/MS (m/z): 488 (M+H)+.

Workup

  1. temperatureThe following morning the mixture was cooled to rt
  2. filtrationfiltered through a plug of celite
  3. washwashing with EtOAc
  4. customThe volatiles were removed under reduced pressure
  5. washeluting with a range of 5-45% EtOAc/Hex over 13 CV

Sources & evidence

ORD record
ord-4774a8c4a4d0477caf73001cb598d691
Source dataset
uspto-grants-2015_04
Patent number
US09006228B2

Reaction notes

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