Diisopropylethylamine → 2-[3-(2,2-Difluoro-2-phenylacetylamino)-2-fluoro-6-nitrophenyl]ethyl acetate

HRID 2184190Notes

Reaction equation

HRID 2184190 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:38])([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:29](Cl)=[O:30]>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:27])([F:38])[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:17]=1[F:26])(=[O:12])[CH3:11]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 224753152,2-Difluoro-2-phenylacetyl chlorideHCID 224753492-(3-Amino-2-fluoro-6-nitrophenyl)ethyl acetate

Product 1

HCID 224753302-[3-(2,2-Difluoro-2-phenylacetylamino)-2-fluoro-6-nitrophenyl]ethyl acetateYield 92.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of DIEA (1.49 mL, 8.55 mmol) and 2-(3-amino-2-fluoro-6-nitrophenyl)ethyl acetate (690 mg, 2.85 mmol), as prepared in the preceding step, in DCM (6 mL) was added a solution of 2,2-difluoro-2-phenylacetyl chloride (0.99 g, 5.20 mmol), as prepared according to the procedure of step 3 of Example 1, in DCM (3 mL). After stirring for 24 hours, the mixture was concentrated, and partitioned between DCM and H2O. The organic layer was separated, and the aqueous layer extracted with DCM. The organic layers were combined, washed with H2O and brine, dried over Na2SO4, concentrated, and flash chromatographed on silica gel eluting with EtOAc/DCM (0, 2.5, and 5%) to give the title compound (1.04 g, 92% yield) as an orange oil. 1H-NMR (400 MHz, CDCl3) δ 8.49-8.43 (m, 2H), 7.87 (d, J=9.2 Hz, 1H), 6.68 (d, J=7.1 Hz, 2H), 7.55-7.49 (m, 3H), 4.35 (t, J=6.4 Hz, 2H), 3.37 (dt, J=6.3, 2.3 Hz, 2H), 2.01 (s, 3H).

Workup

  1. customas prepared
  2. concentrationthe mixture was concentrated
  3. custompartitioned between DCM and H2O
  4. customThe organic layer was separated
  5. extractionthe aqueous layer extracted with DCM
  6. washwashed with H2O and brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customflash chromatographed on silica gel eluting with EtOAc/DCM (0, 2.5, and 5%)

Sources & evidence

ORD record
ord-b79a66e2996f4125bfa23cdb4e8da622
Source dataset
uspto-grants-2005_05
Patent number
US06900231B2

Reaction notes

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