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

HRID 2064429Notes

Reaction equation

HRID 2064429 reaction equation
[C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]#N)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C([Mg]Cl)(C)C.[CH2:26]([Mg]Cl)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C1C[O:38]CC1>>[C:27]1([CH2:26][C:18]([C:15]2[CH:16]=[CH:17][C:12]([C:8]3([NH:7][C:6](=[O:20])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:11][CH2:10][CH2:9]3)=[CH:13][CH:14]=2)=[O:38])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

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

Conditions

Temperature
0 °C

Procedure

A solution of tert-butyl[1-(4-cyanophenyl)cyclobutyl]carbamate (1-2) (16.6 g, 61.0 mmol) in anhydrous THF (300 mL) was cooled to −78° C. while stirring under an atmosphere of nitrogen. Then a 2.0 M solution isopropylmagnesium chloride in THF (30.5 mL, 61.0 mmol) was added dropwise over 5 minutes. The reaction mixture was permitted to stir at −78° C. under an atmosphere of nitrogen for 10 minutes. Then a 2.0 M solution of benzylmagnesium chloride in THF (116 mL, 232 mmol) was added dropwise over 10 minutes. The reaction mixture was permitted to warm to 0° C. After 2 hours the reaction mixture was quenched at 0° C. by addition of a saturated solution of ammonium chloride. The reaction was permitted to warm to room temperature, suspended in ethyl acetate, washed with a saturated solution of ammonium chloride, a saturated solution of sodium bicarbonate, followed by water, brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue was purified by silica gel chromatography (1-40% EtOAc/5% DCM/Hexane) to give tert-butyl {1-[4-(phenylacetyl)phenyl]cyclobutyl}carbamate (1-3) as a waxy off-white solid. HRMS (M+Na)+: observed=388.1892, calculated=388.1883.

Workup

  1. stirringto stir at −78° C. under an atmosphere of nitrogen for 10 minutes
  2. customAfter 2 hours the reaction mixture was quenched at 0° C. by addition of a saturated solution of ammonium chloride
  3. temperatureto warm to room temperature
  4. washwashed with a saturated solution of ammonium chloride
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by silica gel chromatography (1-40% EtOAc/5% DCM/Hexane)

Sources & evidence

ORD record
ord-745dbc1d6b364aadaf15833981d2fbc1
Source dataset
uspto-grants-2012_10
Patent number
US08288407B2

Reaction notes

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