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Ammonium Acetate → Isopropyl 4-[1-{4-[[di(tert-butoxy)phosphoryl](difluoro)methyl]benzyl}-2-(4-fluorophenyl)-2-oxoethyl]benzoate

HRID 1371026
Notes
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Reaction equation

HRID 1371026 reaction equation
[CH:1]([O:4][C:5](=[O:22])[C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=[O:14])=[CH:8][CH:7]=1)([CH3:3])[CH3:2].CC(C)([O-])C.[K+].Br[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]([P:40](=[O:51])([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])([F:39])[F:38])=[CH:33][CH:32]=1.C([O-])(=O)C.[NH4+]>C1COCC1>[C:47]([O:46][P:40]([C:37]([F:39])([F:38])[C:34]1[CH:35]=[CH:36][C:31]([CH2:30][CH:12]([C:9]2[CH:10]=[CH:11][C:6]([C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[O:22])=[CH:7][CH:8]=2)[C:13]([C:15]2[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=2)=[O:14])=[CH:32][CH:33]=1)([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:51])([CH3:48])([CH3:49])[CH3:50]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 517165Ammonium AcetateHCID 15922636Di(tert-butyl) [4-(bromomethyl)phenyl](difluoro)methylphosphonateHCID 18510263Isopropyl-4-[2-(4-fluorophenyl)-2-oxoethyl]benzoate2×HCID 23665647Potassium tert-butoxide

Product 1

HCID 18510274Isopropyl 4-[1-{4-[[di(tert-butoxy)phosphoryl](difluoro)methyl]benzyl}-2-(4-fluorophenyl)-2-oxoethyl]benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of isopropyl-4-[2-(4-fluorophenyl)-2-oxoethyl]benzoate (0.130 g, 0.433 mmol), (Example 4, Step 1) 18-crown-6 (0.03 g) in THF (2.2 ml ) at −2020 C. was added a solution of potassium tert-butoxide 1 M in THF (0.475 ml). To the reaction mixture was added a solution of di(tert-butyl) [4-(bromomethyl)phenyl](difluoro)methylphosphonate (0.196 g, 0.475 mmol) in THF (5 ml). The reaction was stirred at room temperature for 1 hour, and then saturated ammonium acetate solution (20 ml) was added and the mixture was extracted with ethyl acetate (20 ml). The organic phase was washed with brine, dried over sodium sulfate, filtered, and evaporated to dryness. The residue was purified by flash chromatography using hexane/ethyl acetate 15% plus 1% triethylamine giving 0.05 g of the title compound.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (20 ml)
  2. washThe organic phase was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-311973521cb841a19e31eef3ae7333c2
Source dataset
uspto-grants-2003_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06583126B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes