1-(Diphenylmethyl)azetidin-3-one → HCID 71623197, compound

HRID 1961540Notes

Reaction equation

HRID 1961540 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[CH2:13][C:12]([C:18]3[CH:23]=[C:22]([Cl:24])[C:21]([Cl:25])=[C:20]([Cl:26])[CH:19]=3)([C:14]([F:17])([F:16])[F:15])[O:11][N:10]=2)[CH:5]=[CH:6][C:7]=1I.C([Mg]Cl)(C)C.[CH:32]([N:45]1[CH2:48][C:47](=[O:49])[CH2:46]1)([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C1COCC1>[CH:32]([N:45]1[CH2:48][C:47]([C:7]2[CH:6]=[CH:5][C:4]([C:9]3[CH2:13][C:12]([C:18]4[CH:23]=[C:22]([Cl:24])[C:21]([Cl:25])=[C:20]([Cl:26])[CH:19]=4)([C:14]([F:17])([F:16])[F:15])[O:11][N:10]=3)=[CH:3][C:2]=2[Br:1])([OH:49])[CH2:46]1)([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

5

Reactant 3

HCID 37355581-(Diphenylmethyl)azetidin-3-oneHCID 71623196HCID 71623196, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 71623197HCID 71623197, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

In an oven-dried flask containing 3-(3-bromo-4-iodophenyl)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole (Preparation 27, 1000 mg, 1.67 mmol) in THF (25 mL) at −40° C. was slowly added isopropyl magnesium chloride (1.7 mL of 2.0M solution). The reaction was stirred at approx. −40° C. for 1.5 under nitrogen. 1-benzhydrylazetidin-3-one (520 mg in 4 mL THF) was slowly added. The reaction was stirred at −40° C. for an additional 30 minutes and allowed to warm to room temperature. Stirring was continued for 2 hours at room temperature. The reaction was quenched with saturated NH4Cl and extracted with EtOAc (2×75 mL). The combined organic phase was dried (Na2SO4) and concentrated under vacuum. The crude material was chromatographed (40 g Redi-Sep column) eluting from 100% heptane to 60:40 EtOAc:heptane, collecting the intermediate (615 mg, 52%) as a glass. 1HNMR (CDCl3): 7.87 (1H), 7.66-7.63 (3H), 7.45 (4H), 7.36-7.21 (7H), 4.39 (1H), 4.07 (1H), 3.73-3.58 (5H), 3.06 (1H); m/z (Cl) 711 ([M+H]+.

Workup

  1. stirringThe reaction was stirred at −40° C. for an additional 30 minutes
  2. temperatureto warm to room temperature
  3. stirringStirring
  4. customThe reaction was quenched with saturated NH4Cl
  5. extractionextracted with EtOAc (2×75 mL)
  6. dry with materialThe combined organic phase was dried (Na2SO4)
  7. concentrationconcentrated under vacuum
  8. customThe crude material was chromatographed (40 g Redi-Sep column)
  9. washeluting from 100% heptane to 60:40 EtOAc
  10. customheptane, collecting the intermediate (615 mg, 52%) as a glass

Sources & evidence

ORD record
ord-785efeaa2d8a45079b78c660d0e1643d
Source dataset
uspto-grants-2013_04
Patent number
US08415310B2

Reaction notes

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