Diisopropylethylamine → Tert-butyl 2-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)carbonyl]morpholine-4-carboxylate

HRID 603245Notes

Reaction equation

HRID 603245 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([NH:10][C:11]([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[O:12])[CH:6]=[CH:7][C:8]=1[Cl:9].[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][O:29][CH:28]([C:32](O)=[O:33])[CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1>[Cl:2][C:3]1[CH:4]=[C:5]([NH:10][C:11]([N:13]2[CH2:18][CH2:17][N:16]([C:32]([CH:28]3[O:29][CH2:30][CH2:31][N:26]([C:24]([O:23][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:25])[CH2:27]3)=[O:33])[CH2:15][CH2:14]2)=[O:12])[CH:6]=[CH:7][C:8]=1[Cl:9]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27559654-((Tert-butoxy)carbonyl)morpholine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 46743200N-(3,4-dichlorophenyl)piperazine-1-carboxamide hydrochloride

Product 1

HCID 57656874Tert-butyl 2-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)carbonyl]morpholine-4-carboxylateYield 123.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-(3,4-Dichlorophenyl)piperazine-1-carboxamide hydrochloride (467 mg) and 4-(tert-butoxycarbonyl)morpholine-2-carboxylic acid (347 mg) were dissolved in dry THF (10 mL) followed by addition of N,N-diisopropylethylamine (0.52 ml) and HATU (628 mg) and the reaction was stirred for 4 h. The solvent was evaporated under reduced pressure then redissolved in ethyl acetate (50 ml) followed by washing with sat. aqueous NaHCO3 (20 ml), 10% w/v citric acid (aq.) (15 ml) and brine (15 ml). The organic layer was dried (MgSO4), filtered and evaporated. Purification by chromatography (1:1 EtOAc:hexanes 1:1 to EtOAc neat) afforded the title compound (900 mg) as an impure foam contaminated with N,N,N′,N′-tetramethylurea. The product was used without further purification.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionthen redissolved in ethyl acetate (50 ml)
  3. washby washing with sat. aqueous NaHCO3 (20 ml), 10%
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by chromatography (1:1 EtOAc:hexanes 1:1 to EtOAc neat)

Sources & evidence

ORD record
ord-892744c13fbb429ca2176d1ce1be0db1
Source dataset
uspto-grants-2011_03
Patent number
US07906645B2

Reaction notes

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