4-Chloroaniline → 1-(1,1-Dimethylethyl) 3-ethyl (3R,4R)-4-[[(4-chlorophenyl)amino]carbonyl]-1,3-pyrrolidinedicarboxylate

HRID 1987179Notes

Reaction equation

HRID 1987179 reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]1[C@@H:10]([C:11]([OH:13])=O)[CH2:9][N:8]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:7]1)=[O:5])[CH3:2].C(N(CC)C(C)C)(C)C.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.[Cl:45][C:46]1[CH:52]=[CH:51][C:49]([NH2:50])=[CH:48][CH:47]=1>C(#N)C>[CH2:1]([O:3][C:4]([C@@H:6]1[C@@H:10]([C:11](=[O:13])[NH:50][C:49]2[CH:51]=[CH:52][C:46]([Cl:45])=[CH:47][CH:48]=2)[CH2:9][N:8]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:7]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 78124-ChloroanilineHCID 81531DiisopropylethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 34180170HCID 34180170, compound

Product 1

HCID 690476271-(1,1-Dimethylethyl) 3-ethyl (3R,4R)-4-[[(4-chlorophenyl)amino]carbonyl]-1,3-pyrrolidinedicarboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

Compound 7a (1 g; 3.48 mmol) is suspended in acetonitrile (7 ml) and N,N-diisopropyl ethyl amin (1.22 ml; 6.96 mmol) is added at 25° C. BOP-Cl (1.772 g; 6.96 mmol) is added as a solid and after stirring for 30 min at 25° C. 4-chloroaniline (0.444 g; 3.48 mmol) is added to the reaction mixture. The mixture is stirred for 18 h at 25° C., evaporated to dryness and dissolved in ethyl acetate (100 ml). The organic phase is washed with saturated aquous Na2CO3 solution (100 ml), 2 N HCl (50 ml), water and brine and dried over Na2SO4. The organic phase is filtered and the filtrate is evaporated to dryness. The crude product is purified by silica gel chromatography. Yield: 0.5 g (36.2%), ESI-MS: m/z=395 [M−H]−, Cl-pattern

Workup

  1. stirringThe mixture is stirred for 18 h at 25° C.
  2. customevaporated to dryness
  3. dissolutiondissolved in ethyl acetate (100 ml)
  4. washThe organic phase is washed with saturated aquous Na2CO3 solution (100 ml), 2 N HCl (50 ml), water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationThe organic phase is filtered
  7. customthe filtrate is evaporated to dryness
  8. customThe crude product is purified by silica gel chromatography

Sources & evidence

ORD record
ord-c482cbc6b71c400c8d52dc7811ac1dff
Source dataset
uspto-grants-2009_06
Patent number
US07550487B2

Reaction notes

Loading…