4-Chloroaniline → trans-(3RS,4RS)-4-(4-Chlorophenylcarbamoyl)-pyrrolidine-1,3-dicarboxylic Acid 1-tert-butyl Ester

HRID 1987171Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([C:13]([OH:15])=[O:14])[C@H:10]([C:16]([OH:18])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.ON1C2C=CC=CC=2N=N1.C1C=CC2N(O)N=NC=2C=1.[Cl:48][C:49]1[CH:55]=[CH:54][C:52]([NH2:53])=[CH:51][CH:50]=1>C(#N)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][C@@H:10]([C:16](=[O:18])[NH:53][C:52]2[CH:54]=[CH:55][C:49]([Cl:48])=[CH:50][CH:51]=2)[C@H:11]([C:13]([OH:15])=[O:14])[CH2:12]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: 25 °C

Procedure

Compound 1c (2.25 g; 9 mmol) is suspended in acetonitrile (30 ml) and N,N-diisopropyl ethyl amin (3.03 ml; 17 mmol) is added at 25° C. After 20 min a clear solution is obtained and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDCI (2.0 g; 10 mmol) and 1-hydroxybenzotriazole HOBt (1.41 g; 10 mmol) is added. After stirring for 30 min at 25° C. 4-chloroaniline (1.11 g; 9 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 0.1 N HCl (2×100 ml), water and brine and dried over Na2SO4. The organic phase is filtered and the filtrate is evaporated to dryness. Yield: 1.08 g (33.7%), ESI-MS: m/z=368 [M−H]−, Cl-pattern

Workup

customAfter 20 min a clear solution is obtained
stirringThe mixture is stirred for 18 h at 25° C.
customevaporated to dryness
dissolutiondissolved in ethyl acetate (100 ml)
washThe organic phase is washed with 0.1 N HCl (2×100 ml), water and brine
dry with materialdried over Na2SO4
filtrationThe organic phase is filtered
customthe filtrate is evaporated to dryness

Sources & evidence

ORD record: ord-1facb16bf5e34afe91c4b2934370f8a8
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07550487B2

Reaction notes

Loading…