1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-[4-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoyl]piperazin-2-one

HRID 389990Notes

Reaction equation

HRID 389990 reaction equation
C(N(CC)C(C)C)(C)C.[NH:10]1[CH2:15][CH2:14][NH:13][CH2:12][C:11]1=[O:16].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH2:38]([C:40]1[C:56]([F:57])=[CH:55][C:43]([O:44][C:45]2[CH:53]=[CH:52][C:48]([C:49](O)=[O:50])=[CH:47][C:46]=2[F:54])=[C:42]([O:58][CH3:59])[CH:41]=1)[CH3:39].C(=O)([O-])O.[Na+]>ClCCl>[CH2:38]([C:40]1[C:56]([F:57])=[CH:55][C:43]([O:44][C:45]2[CH:53]=[CH:52][C:48]([C:49]([N:13]3[CH2:14][CH2:15][NH:10][C:11](=[O:16])[CH2:12]3)=[O:50])=[CH:47][C:46]=2[F:54])=[C:42]([O:58][CH3:59])[CH:41]=1)[CH3:39]

Participants

8

Reactant 6

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 231360Piperazin-2-oneHCID 516892Sodium BicarbonateHCID 671160464-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoic acid

Product 1

HCID 671162484-[4-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoyl]piperazin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N-Diisopropylethylamine (2.8 mL, 16 mmol), piperazin-2-one (780 mg, 7.8 mmol), EDCI (1.5 g, 7.8 mmol) and HOBt (1.05 g, 7.8 mmol) were successively added to a solution of 4-(4-ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoic acid (which may be prepared in accordance with the experimental described in Example 4, step 4; 2.0 g, 6.5 mmol) in dichloromethane (22 mL). The reaction mixture was stirred at room temperature overnight and then diluted by addition of dichloromethane (50 mL) and a saturated solution of sodium hydrogen carbonate (50 mL). After separation, the aqueous layer was extracted with dichloromethane (2×50 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated under vacuum. The residue was purified by chromatography on silica gel, using dichloromethane/petroleum ether (80/20) to dichloromethane (100%) to dichloromethane/methanol (98:2 to 95:5) as eluent. The title product was obtained as a yellow solid (2.0 g, 80%).

Workup

  1. custommay be prepared in accordance with the
  2. customAfter separation
  3. extractionthe aqueous layer was extracted with dichloromethane (2×50 mL)
  4. dry with materialThe combined organic phases were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-df76e572cbd54892a100dbf86fb037fd
Source dataset
uspto-grants-2013_02
Patent number
US08383621B2

Reaction notes

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