Tetrahydrofuran → tert-Butyl {1-[4-(phenylacetyl)phenyl]cyclobutyl}carbamate

HRID 2362148Notes

Reaction equation

HRID 2362148 reaction equation
C([Mg]Cl)(C)C.[C:6]([O:10][C:11](=[O:25])[NH:12][C:13]1([C:17]2[CH:22]=[CH:21][C:20]([C:23]#N)=[CH:19][CH:18]=2)[CH2:16][CH2:15][CH2:14]1)([CH3:9])([CH3:8])[CH3:7].[CH2:26]([Mg]Cl)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C1C[O:38]CC1>>[C:6]([O:10][C:11](=[O:25])[NH:12][C:13]1([C:17]2[CH:22]=[CH:21][C:20]([C:23](=[O:38])[CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:19][CH:18]=2)[CH2:16][CH2:15][CH2:14]1)([CH3:9])([CH3:8])[CH3:7]

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 46856381tert-Butyl [1-(4-cyanophenyl)cyclobutyl]carbamateHCID 178418336HCID 178418336, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 57805516tert-Butyl {1-[4-(phenylacetyl)phenyl]cyclobutyl}carbamate

Procedure

A solution of i-PrMgCl (9.65 mL, 19.3 mmol) in THF was added dropwise to a solution of compound 1-2 (5.24 g, 19.3 mmol) in dry THF at −5.deg.C. After stirring for 20 min, a solution of BnMgCl (29 mL, 2M, 58 mmol) in THF was added dropwise to the reaction mixture. After completion of addition, the reaction mixture was stirred for 1 h at 0.deg.C, then warmed slowly to room temperature, and stirred for another 1 h. The reaction was quenched with saturated NH4 Cl solution, extracted with ethyl acetate. Separated and collected the organic layer, and the aqueous solution was washed EA for two times. The combined organic layer was washed with brine, dried and concentrated in vacuo to get the crude product, which was purified by silica chromatography to give 5.5 g of ketone 1-3.

Workup

  1. additionAfter completion of addition
  2. stirringthe reaction mixture was stirred for 1 h at 0.deg.C
  3. stirringstirred for another 1 h
  4. customThe reaction was quenched with saturated NH4 Cl solution
  5. extractionextracted with ethyl acetate
  6. customSeparated
  7. customcollected the organic layer
  8. washthe aqueous solution was washed EA for two times
  9. washThe combined organic layer was washed with brine
  10. customdried
  11. concentrationconcentrated in vacuo
  12. customto get the crude product, which
  13. customwas purified by silica chromatography

Sources & evidence

ORD record
ord-897af6df82144b2f9a01aa52567396d6
Source dataset
uspto-grants-2014_04
Patent number
US08691825B2

Reaction notes

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