Chlorosuccinimide → Tert-butyl 3-fluoro-3-(4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)phenyl)azetidine-1-carboxylate

HRID 1961528Notes

Reaction equation

HRID 1961528 reaction equation
[F:1][C:2]1([C:13]2[CH:18]=[CH:17][C:16]([CH:19]=[N:20][OH:21])=[CH:15][CH:14]=2)[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1.C1C(=O)N(Cl)C(=O)C1.[Cl:30][C:31]1[CH:36]=[C:35]([C:37](=[CH2:42])[C:38]([F:41])([F:40])[F:39])[CH:34]=[C:33]([Cl:43])[C:32]=1[Cl:44].C(=O)(O)[O-].[K+]>CCOC(C)=O.CN(C=O)C>[F:1][C:2]1([C:13]2[CH:14]=[CH:15][C:16]([C:19]3[CH2:42][C:37]([C:35]4[CH:34]=[C:33]([Cl:43])[C:32]([Cl:44])=[C:31]([Cl:30])[CH:36]=4)([C:38]([F:41])([F:40])[F:39])[O:21][N:20]=3)=[CH:17][CH:18]=2)[CH2:3][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:5]1

Participants

7

Reactant 4

HCID 31398ChlorosuccinimideHCID 516893Potassium BicarbonateHCID 498201551,2,3-Trichloro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzeneHCID 76661477Tert-butyl 3-fluoro-3-(4-((hydroxyimino)methyl)phenyl)azetidine-1-carboxylate

Product 1

HCID 78146950Tert-butyl 3-fluoro-3-(4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)phenyl)azetidine-1-carboxylateYield 56.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a DMF (8 mL) solution of tert-butyl 3-fluoro-3-(4-((hydroxyimino)methyl)-phenyl)azetidine-1-carboxylate (Preparation 7, 486 mg, 1.65 mmol) was added NCS (232 mg, 1.65 mmol) in two portions over 10 minutes. The reaction was stirred at room temperature overnight. The reaction was diluted with EtOAc (8 mL) and 1,2,3-trichloro-5-(1,1,1-trifluoroprop-2-en-2-yl)benzene (546 mg, 1.98 mmol) was added, followed by potassium bicarbonate (248 mg, 2.48 mmol). The reaction was stirred at room temperature for 3 days. The reaction was concentrated under vacuum. The residue was partitioned between EtOAc (50 mL) and water (50 mL). The aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layers were dried and condensed. The crude material was adsorbed on silica and chromatographed on a 40 g silica column eluting with a gradient of 0%-40% EtOAc/hexanes over 20 minutes. Fractions containing the desired material were combined and concentrated to yield 526 mg of a white solid. 1H NMR (CDCl3) δ 7.74 (d, 2H), 7.67 (s, 2H), 7.56 (d, 2H), 4.39-4.51 (m, 2H), 4.24 (m 2H), 4.12 (d, 1H), 3.72 (d, 1H), 1.5 (s, 9H).

Workup

  1. additionwas added
  2. stirringThe reaction was stirred at room temperature for 3 days
  3. concentrationThe reaction was concentrated under vacuum
  4. customThe residue was partitioned between EtOAc (50 mL) and water (50 mL)
  5. extractionThe aqueous layer was extracted with EtOAc (3×50 mL)
  6. customThe combined organic layers were dried
  7. customcondensed
  8. customchromatographed on a 40 g silica column
  9. washeluting with a gradient of 0%-40% EtOAc/hexanes over 20 minutes
  10. additionFractions containing the desired material
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-3992ac6b52dd44d8b74aee324afad69c
Source dataset
uspto-grants-2013_04
Patent number
US08415310B2

Reaction notes

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