Triethylamine → HCID 69214775, compound

HRID 1392165Notes

Reaction equation

HRID 1392165 reaction equation
CCN(CC)CC.Cl.[CH3:9][O:10][C:11](=[O:17])[C@@H:12]1[CH2:16][CH2:15][CH2:14][NH:13]1.[Cl:18][C:19]1[CH:20]=[C:21]([N:26]=[C:27]=[O:28])[CH:22]=[C:23]([Cl:25])[CH:24]=1>C(Cl)Cl>[CH3:9][O:10][C:11](=[O:17])[C@@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[C:27](=[O:28])[NH:26][C:21]1[CH:22]=[C:23]([Cl:25])[CH:24]=[C:19]([Cl:18])[CH:20]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 944603,5-Dichlorophenyl isocyanateHCID 2733200methyl L-prolinate hydrochloride

Product 1

HCID 69214775HCID 69214775, compoundYield 90.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Et3N (1.7 mL) was added to an ice-cold solution of (S)-proline methyl ester hydrochloride (1.31 g) and 3,5-dichlorophenylisocyanate (1.97 g) in CH2Cl2 (40 mL). The mixture was stirred for 3 hours. It was washed with water, brine, dried (MgSO4), filtered, and concentrated. Purification by chromatography (Silica gel: EtOAc/hexane: 1/3) afforded (S)—N—[N-(3,5-dichlorophenyl)carbamoyl]proline methyl ester (2.27 g). mp. 110-112° C.; MS (m/z) 339 (M++Na). (2) A solution of the compound obtained above (14.3 g) in toluene (100 mL) containing p-toluenesulfonic acid (0.5 g) was refluxed for 2 hours. The solution was diluted with EtOAc and was washed with satd. NaHCO3, water, brine, dried (MgSO4), filtered, and concentrated. Purification by chromatography (Silica gel: CHCL3/MeOH: 10/1) and recrystallization from EtOH afforded 8.87 g of (S)-3-(3,5-dichlorophenyl)-1,3-diazabicyclo[3.3.0]octane-2,4-dione. mp. 169° C.; MS (m/z) 307 (M++Na). (3) A solution of n-BuLi (2.2 mL) in hexane (1.6 N) was added to a solution of diisopropylamine (0.381 g) in THF (5 mL) at −78° C. After 15 minutes, a solution of the compound obtained above (0.894 g) in THF (8 mL) was added to the mixture. HMPA (8 mL) and additional THF (8 mL) were added to the mixture. After 35 minutes, a solution of 4-(bromomethyl)benzonitrile (0.697 g) in THF (8 mL) was added and the mixture stirred for 30 minutes at that temperature. The mixture was slowly warmed to room temperature, stirred for 30 minutes and finally quenched with 0.5 N HCl (10 mL). The mixture was diluted with water and extracted with EtOAc. The extract was washed with water, brine, dried (Na2SO4), filtered, and concentrated. Purification by chromatography (Silica gel: EtOAc/hexane: 1/2, Chromatotron) afforded the titled compound (0.833 g). MS (m/z) 422 (M++Na).

Workup

  1. washIt was washed with water, brine
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by chromatography (Silica gel: EtOAc/hexane: 1/3)

Sources & evidence

ORD record
ord-3431afc51d9540f58da43d1087c4cf22
Source dataset
uspto-grants-2008_03
Patent number
US07342012B2

Reaction notes

Loading…