Triethylamine → HCID 22821052, compound

HRID 1759615Notes

Reaction equation

HRID 1759615 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15](O)=[O:16])[C:10](=[O:18])[CH:9]1[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:22][CH:21]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.C(OC(Cl)=O)C(C)C.Cl.[NH2:50][CH2:51][C:52]([NH:54][C@H:55]([C:63]([NH:65][CH3:66])=[O:64])[CH2:56][C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)=[O:53]>O.C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]([NH:50][CH2:51][C:52]([NH:54][C@H:55]([C:63]([NH:65][CH3:66])=[O:64])[CH2:56][C:57]2[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=2)=[O:53])=[O:16])[C:10](=[O:18])[CH:9]1[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[CH:22][CH:21]=1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 62365Isobutyl chloroformateHCID 20437871HCID 20437871, compoundHCID 22821046HCID 22821046, compound

Product 1

HCID 22821052HCID 22821052, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

To a solution of piperazinone acetic acid 5a (0.45 g, 1.0×10-3 mole) and dry THF (3 ml) at -10° C. under argon is added in turn Et3N (0.16 ml, 1.1×10-3 mole) and isobutylchloroformate (0.15 ml, 1.1×10-3 mole). After stirring 10 minutes at -10° C., a freshly neutralized solution of glycyl-L-phenylalanine methyl amide 9a hydrochloride (0.30 g, 1.1×10-3 mole), Et3N (0.28 ml, 2.0×10-3 mole), THF (3 ml), and H2O (1.5 ml) is added in one portion. The cooling bath is then removed and the reaction allowed to warm to room temperature. After stirring overnight the reaction is quenched into 0.5 M aqueous HCl. The aqueous mixture is extracted with Et2O (2 times) and CH2Cl2 (2 times). The ethereal extracts are combined and washed with saturated aqueous NaHCO3 as are the CH2Cl2 extracts. The ethereal and CH2Cl2 extracts are then combined and dried over Na2SO4. Filtration of the drying agent and evaporation of the filtrate give 10a which is purified by chromatography, and the structure corroborated by NMR. NMR (CDCl3) δ1.26 (S, 9, t-boc), 2.64 (d, 3, methylamide), 3.08, 3.90 (m, 12, methylenes), 4.68 (m, 2, C3 -H and phenylala-CH), 4.98 (S, 2, benzyloxy methylene), 6.6-7.8 (m, 17, aromatic and amide NH's).

Workup

  1. customThe cooling bath is then removed
  2. temperatureto warm to room temperature
  3. stirringAfter stirring overnight the reaction
  4. customis quenched into 0.5 M aqueous HCl
  5. extractionThe aqueous mixture is extracted with Et2O (2 times) and CH2Cl2 (2 times)
  6. washwashed with saturated aqueous NaHCO3
  7. dry with materialdried over Na2SO4
  8. filtrationFiltration of the drying agent and evaporation of the filtrate

Sources & evidence

ORD record
ord-cdb754ee9b62485ba7ddebbace008708
Source dataset
uspto-grants-1982_07
Patent number
US04341698

Reaction notes

Loading…