4-Methylmorpholine → HCID 131723057, compound

HRID 2271221Notes

Reaction equation

HRID 2271221 reaction equation
ClC(OCC(C)C)=O.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([CH2:22][CH2:23][CH:24]([CH2:32][CH2:33][CH:34]2[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]2)[C:25]([NH:27][CH2:28][C:29](O)=[O:30])=[O:26])[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].CN1CCOCC1.Cl.[NH2:55][CH2:56][C@H:57]([NH:63][C:64]([O:66][CH2:67][C:68]1[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=1)=[O:65])[C:58]([O:60][CH2:61][CH3:62])=[O:59]>C(OCC)(=O)C>[C:43]([O:42][C:40]([N:37]1[CH2:36][CH2:35][CH:34]([CH2:33][CH2:32][CH:24]([C:25](=[O:26])[NH:27][CH2:28][C:29](=[O:30])[NH:55][CH2:56][C@@H:57]([C:58]([O:60][CH2:61][CH3:62])=[O:59])[NH:63][C:64](=[O:65])[O:66][CH2:67][C:68]2[CH:69]=[CH:70][CH:71]=[CH:72][CH:73]=2)[CH2:23][CH2:22][CH:19]2[CH2:20][CH2:21][N:16]([C:14]([O:13][C:9]([CH3:10])([CH3:11])[CH3:12])=[O:15])[CH2:17][CH2:18]2)[CH2:39][CH2:38]1)=[O:41])([CH3:44])([CH3:45])[CH3:46]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 15433187HCID 15433187, compound2×HCID 22882881Ethyl (2s)-3-amino-2-{[(benzyloxy)carbonyl]amino}propanoate hydrochloride

Product 1

HCID 131723057HCID 131723057, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Isobutyl chloroformate (13 g, 95.2 mmol) is added, at room temperature, to a solution of 2-[(4-[1-(tert-butoxycarbonyl)-4-piperidyl]-2-{2-[1-(tert-butoxycarbonyl)-4-piperidyl]ethyl}butanoyl)amino]acetic acid (compound 4) (46 g, 85.2 mmol) in 550 ml of ethyl acetate and N-methylmorpholine (19 g, 188 mmol), and a suspension is obtained. After stirring for 20 minutes, ethyl (2S)-3-amino-2-{[(benzyloxy)carbonyl]amino}propanoate hydrochloride (26.3 g, 86.9 mmol) is added. Stirring is continued for 18 hours at room temperature and the reaction medium is then washed with water, with 1N hydrochloric acid and with water and then dried over sodium sulphate and evaporated to give the crude product, which is purified by flash chromatography (20/1 dichloromethane/methanol) to give 61 g of a white solid.

Workup

  1. customa suspension is obtained
  2. stirringStirring
  3. waitis continued for 18 hours at room temperature
  4. washthe reaction medium is then washed with water, with 1N hydrochloric acid and with water
  5. dry with materialdried over sodium sulphate
  6. customevaporated
  7. customto give the crude product, which
  8. customis purified by flash chromatography (20/1 dichloromethane/methanol)

Sources & evidence

ORD record
ord-3cda9dc1a2b7492facfdc36e8767f982
Source dataset
uspto-grants-2001_12
Patent number
US06333338B1

Reaction notes

Loading…