Phenyl isocyanate → Methyl 3-[2-(4'-fluoro-3,3',5-trimethyl[1,1'-biphenyl]-2-yl)ethyl]-4,5-dihydro-5-isoxazoleacetate

HRID 344826

Reaction equation

HRID 344826 reaction equation
[C:1]([O:6][CH3:7])(=[O:5])[CH2:2][CH:3]=[CH2:4].C1(N=C=O)C=CC=CC=1.[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[C:28]([CH3:30])[CH:27]=[C:26]([CH3:31])[C:25]=2[CH2:32][CH2:33][CH2:34][N+:35]([O-])=[O:36])=[CH:20][C:19]=1[CH3:38].C(N(CC)CC)C>C1(C)C=CC=CC=1.C(N(CC)CC)C>[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[C:28]([CH3:30])[CH:27]=[C:26]([CH3:31])[C:25]=2[CH2:32][CH2:33][C:34]2[CH2:4][CH:3]([CH2:2][C:1]([O:6][CH3:7])=[O:5])[O:36][N:35]=2)=[CH:20][C:19]=1[CH3:38]

Participants

7

Reactant 4

HCID 7672Phenyl isocyanate2×HCID 8471TriethylamineHCID 77314Methyl 3-butenoate2×HCID 540403614'-Fluoro-3,3',5-trimethyl-2-(3-nitropropyl)-1,1'-biphenyl

Product 1

HCID 54381644Methyl 3-[2-(4'-fluoro-3,3',5-trimethyl[1,1'-biphenyl]-2-yl)ethyl]-4,5-dihydro-5-isoxazoleacetateYield 71.2%

Reagents, catalysts & solvents 2

HCID 8471TriethylamineCatalystHCID 1140TolueneSolvent2×

Procedure

A solution of 0.1 g (1.0 mmol) of methyl 3-butenoate and 0.174 ml (1.6 mmol) of phenyl isocyanate in 1 ml of toluene was added with stirring to a solution of 0.240 g (0.8 mmol) of the nitropropyl compound from Step D and 2 drops of triethylamine in 1 ml of toluene. The resulting mixture was stirred at room temperature for 3 hours. Additional quantities of methyl 3-butenoate (0.1 ml), triethylamine (0.1 ml) and phenyl isocyanate (0.15 ml) were added successively and stirring was continued overnight (18 hours). The mixture was filtered and the filtrate was concentrated in vacuo to a residue which was purified by flash chromatography on silica gel (230-400 mesh), first being eluted with methylene chloride to remove the impurities. Continued elution with acetone/methylene chloride (1:50, v/v) gave the desired product (0.218 g, 0.57 mmol, 71%) as a pale viscous oil. nmr (CDCl3) δ: 2.28 (6H, s), 2.32 (3H, s), 2.2-3.0 (6H, m), 3.70 (3H, s), 4.6-5.0 (H, m), 6.85 (H, bs), 7.0-7.2 (4H, m). IR (neat) 1735 cm-1

Workup

  1. stirringstirring
  2. waitwas continued overnight
  3. custom(18 hours)
  4. filtrationThe mixture was filtered
  5. concentrationthe filtrate was concentrated in vacuo to a residue which
  6. customwas purified by flash chromatography on silica gel (230-400 mesh)
  7. washfirst being eluted with methylene chloride
  8. customto remove the impurities
  9. washContinued elution with acetone/methylene chloride (1:50

Sources & evidence

ORD record
ord-aa311eec656c4fe7b866b87122ba700a
Source dataset
uspto-grants-1991_10
Patent number
US05053525

Linked notes

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