Diclofenac → Diclofenac lactam

HRID 514971Notes

Reaction equation

HRID 514971 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][C:17]([OH:19])=[O:18].[C:20]([NH:27][CH2:28][CH2:29]O)([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:23]([O:22][C:20]([NH:27][CH2:28][CH2:29][O:18][C:17](=[O:19])[CH2:16][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[NH:9][C:3]1[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=1[Cl:8])=[O:21])([CH3:26])([CH3:25])[CH3:24].[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:10]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:16][C:17]1=[O:19]

Participants

7

Reactant 3

HCID 3033Diclofenac2×HCID 10868DicyclohexylcarbodiimideHCID 2733206tert-butyl N-(2-hydroxyethyl)carbamate

Product 2

HCID 27211Diclofenac lactamHCID 118302985[2-(2,6-Dichloro-phenylamino)-phenyl]-acetic acid 2-tert-butoxycarbonylamino-ethyl ester

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of [2-(2,6-Dichloro-phenylamino)-phenyl]-acetic acid] 2 (4.0 g, 0.01 mol, 1 eq) and N-BOC-Ethanolamine (2.39 g, 0.01 mol) in DCM (70 mL) was added DMAP (0.16 g, 0.001 mol) at rt. To this mixture was added DCC (5.5 g, 0.02 mol) in DCM (30 mL) drop-wise at 0-5° C. and resulting mixture was stirred at room temperature for 1 h. Reaction was monitored by TLC. After completion, reaction mixture was filtered and the solvent was removed under reduced pressure. Residue was dissolved in water (100 mL) and extracted with DCM (2×50 mL). Combined organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure to obtained crude compound which was washed with hexane (2×20 mL), dried to get 6.0 g crude of Compound 4 and cyclized compound 1 as an off white solid. This mixture was used in the next step without any further purification: Mass: 439.3 (M++H).

Workup

  1. customresulting mixture
  2. customReaction
  3. customAfter completion, reaction mixture
  4. filtrationwas filtered
  5. customthe solvent was removed under reduced pressure
  6. dissolutionResidue was dissolved in water (100 mL)
  7. extractionextracted with DCM (2×50 mL)
  8. dry with materialCombined organic layer was dried over anhydrous Na2SO4
  9. customevaporated under reduced pressure
  10. customto obtained crude compound which
  11. washwas washed with hexane (2×20 mL)
  12. customdried

Sources & evidence

ORD record
ord-f69bc0c75e3d4f219eeb7d91d2be4197
Source dataset
uspto-grants-2015_08
Patent number
US09108942B1

Reaction notes

Loading…