Oxalyl chloride → 2-{3-[2,2-Difluoro-2-(4-fluoronaphthyl)acetylamino]-2-fluoro-6-nitrophenyl]ethyl Acetate

HRID 2184201Notes

Reaction equation

HRID 2184201 reaction equation
CCN(C(C)C)C(C)C.[C:10]([O:13][CH2:14][CH2:15][C:16]1[C:21]([N+:22]([O-:24])=[O:23])=[CH:20][CH:19]=[C:18]([NH2:25])[C:17]=1[F:26])(=[O:12])[CH3:11].[F:27][C:28]([F:43])([C:32]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:35]([F:42])=[CH:34][CH:33]=1)[C:29](Cl)=[O:30].FC(F)(C1C2C(=CC=CC=2)C(F)=CC=1)C(O)=O.C(Cl)(=O)C(Cl)=O>C(Cl)Cl>[C:10]([O:13][CH2:14][CH2:15][C:16]1[C:21]([N+:22]([O-:24])=[O:23])=[CH:20][CH:19]=[C:18]([NH:25][C:29](=[O:30])[C:28]([F:43])([F:27])[C:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[C:35]([F:42])=[CH:34][CH:33]=2)[C:17]=1[F:26])(=[O:12])[CH3:11]

Participants

7

Reactant 5

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 224753182,2-Difluoro-2-(4-fluoronaphthyl)acetic AcidHCID 224753492-(3-Amino-2-fluoro-6-nitrophenyl)ethyl acetateHCID 224753642,2-Difluoro-2-(4-fluoronaphthyl)acetyl chloride

Product 1

HCID 224753272-{3-[2,2-Difluoro-2-(4-fluoronaphthyl)acetylamino]-2-fluoro-6-nitrophenyl]ethyl AcetateYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of DIEA (7.8 mL) and 2-(3-amino-2-fluoro-6-nitrophenyl)ethyl acetate (4.6 g, 19 mmol), prepared as in step 8 of Example 1, in DCM (60 mL) was added 2,2-difluoro-2-(4-fluoronaphthyl)acetyl chloride (prepared by refluxing 2,2-difluoro-2-(4-fluoronaphthyl)acetic acid, as prepared in the preceding step, with oxalyl chloride) (7.8 g, 30 mmol) in DCM (40 mL). The mixture was stirred at room temperature for 1 hour. Additional DCM (100 mL) was added, and the resulting mixture was washed with 10% citric acid (3×40 mL) and brine, and dried over Na2SO4. After evaporating the solvent, the residue was purified by flash column chromatography eluting with DCM to give the title compound (5.3 g, 61%) as a yellow oil. 1H-NMR (400 MHz, CDCl3) δ 8.45 (m, 2H), 8.21 (d, J=7.0 Hz, 2H), 7.87 (s, 1H), 7.85 (t, J=4.1 Hz, 1H), 7.66 (m, 2H), 7.22 (t, J=8.3 Hz, 1H), 4.34 (t, J=6.4 Hz, 2H), 3.36 (t, J=6.4 Hz, 2H), 2.00 (s, 3H).

Workup

  1. customprepared
  2. washthe resulting mixture was washed with 10% citric acid (3×40 mL) and brine
  3. dry with materialdried over Na2SO4
  4. customAfter evaporating the solvent
  5. customthe residue was purified by flash column chromatography
  6. washeluting with DCM

Sources & evidence

ORD record
ord-0e1ca3525c7449c9ae15168b727fd97c
Source dataset
uspto-grants-2005_05
Patent number
US06900231B2

Reaction notes

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