Cyclobutanone → HCID 10404197, compound

HRID 375809Notes

Reaction equation

HRID 375809 reaction equation
[Cl:1][C:2]1[CH:23]=[CH:22][C:5]2[O:6][C:7]3[CH:21]=[CH:20][CH:19]=[CH:18][C:8]=3[CH2:9][N:10]([C:11]([O:13][C:14](C)([CH3:16])[CH3:15])=[O:12])[C:4]=2[CH:3]=1.[CH:24]([N-]C(C)C)(C)C.[Li+].C1(=O)CCC1>C1COCC1>[Cl:1][C:2]1[CH:23]=[CH:22][C:5]2[O:6][C:7]3[CH:21]=[CH:20][CH:19]=[CH:18][C:8]=3[CH:9]3[C:14]4([CH2:16][CH2:24][CH2:15]4)[O:13][C:11](=[O:12])[N:10]3[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 14496CyclobutanoneHCID 2724682Lithium diisopropylamideHCID 14938748HCID 14938748, compound

Product 1

HCID 10404197HCID 10404197, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 1.0 g (3.0 mmol) of 1 in 20 mL of anhydrous THF was added 1.2 equivalent of lithium diisopropylamide at -78°. After 30 minutes, approximately 2 equivalent of cyclobutanone was added as the electrophile. The stirring was continued for 3 hours at -78°, followed by room temperature overnight, and was quenched with saturated ammonium chloride solution. The mixture was diluted with ethyl acetate, washed with brine and dried with magnesium sulfate or sodium sulfate. Purification by HPLC on silica gel with 7% ethyl acetate/hexane as the eluent followed by lyophilization from acetonitrile/water gave 355 mg (36%) of Compound 21. 1H NMR (CDCl3): δ7.62 (s, 1H, ArH), 7.16-7.40 (m, 6H, ArH), 5.19 (s, 1H, ARCH), 2.75-2.84 (m, 1H, c-butyl), 2.45-2.60 (m, 1H, c-butyl), 2.28-2.42 (m, 1H, c-butyl), 2.12- 2.26 (m, 1H, c-butyl), 1.82-2.00 (m, 1H, c-butyl), 1.30-1.45 (m, 1H, c-butyl). FABMS: m/z 334 (M+Li). HRMS calculated for C18H14NO3LiCl (M+Li) 334.0822, found 334.0867. Analysis Calculated for C18H14NO3Cl: C, 65.96; H, 4.31; N, 4.27; Cl, 10.82. Found: C, 65.86; H, 4.31; N, 4.31; Cl, 10.46.

Workup

  1. waitThe stirring was continued for 3 hours at -78°
  2. waitfollowed by room temperature overnight
  3. customwas quenched with saturated ammonium chloride solution
  4. additionThe mixture was diluted with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried with magnesium sulfate or sodium sulfate
  7. customPurification by HPLC on silica gel with 7% ethyl acetate/hexane as the eluent

Sources & evidence

ORD record
ord-f20168fb50f245d39d8ac02cb798d02c
Source dataset
uspto-grants-1996_01
Patent number
US05488046

Reaction notes

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