1,2-Dichloroethane → N-(tert-Butoxycarbonyl)-3-(tert-butyl)-D-alanyl-3-(3-pyridyl)-L-alanine methyl ester

HRID 2220818Notes

Reaction equation

HRID 2220818 reaction equation
CN1CCOCC1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[C:22]([O:26][C:27]([NH:29][C@@H:30]([C:36]([OH:38])=O)[CH2:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:28])([CH3:25])([CH3:24])[CH3:23].[CH3:39][O:40][C:41](=[O:51])[C@H:42]([CH2:44][C:45]1[CH:46]=[N:47][CH:48]=[CH:49][CH:50]=1)[NH2:43]>ClCCl>[CH3:39][O:40][C:41](=[O:51])[C@H:42]([CH2:44][C:45]1[CH:46]=[N:47][CH:48]=[CH:49][CH:50]=1)[NH:43][C:36](=[O:38])[C@@H:30]([CH2:31][C:32]([CH3:33])([CH3:34])[CH3:35])[NH:29][C:27]([O:26][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:28]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 5706551Methyl (S)-2-amino-3-(pyridin-3-yl)propanoateHCID 7021114(R)-2-((tert-Butoxycarbonyl)amino)-4,4-dimethylpentanoic acid

Product 1

HCID 59709769N-(tert-Butoxycarbonyl)-3-(tert-butyl)-D-alanyl-3-(3-pyridyl)-L-alanine methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N-methylmorpholine (5 equivalents, 6.0 mmol), EDC (2.5 equivalents, 3.0 mmol) and HOBt (2.5 equivalents, 3.0 mmol) are added slowly to a solution of N-(tert-butoxycarbonyl)-3-tert-butyl-D-alanine (1.0 equivalent, 1.2 mmol) and 3-(3-pyridyl)-L-alanine methyl ester (1.0 equivalent, 1.2 mmol) in dry dichloromethane (3 ml) at −30° C. The reaction mixture slowly (approx. 12 h) warms to room temperature, with complete conversion being observed by means of HPLC (method 36). The reaction mixture is worked up by diluting with dichloromethane (20 ml) and washing with saturated sodium bicarbonate solution (10 ml). The organic phase is dried with magnesium sulphate, filtered and concentrated. The crude product is purified by flash chromatography (silica gel, gradient dichloromethane 100% to dichloromethane/methanol: 4/1), resulting in 466 mg (96% of theory) of product.

Workup

  1. customThe reaction mixture slowly (approx. 12 h)
  2. customwarms to room temperature, with complete conversion
  3. washwashing with saturated sodium bicarbonate solution (10 ml)
  4. dry with materialThe organic phase is dried with magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product is purified by flash chromatography (silica gel, gradient dichloromethane 100% to dichloromethane/methanol: 4/1)
  8. customresulting in 466 mg (96% of theory) of product

Sources & evidence

ORD record
ord-96098b95748e45f6bc979c27a525dc70
Source dataset
uspto-grants-2008_05
Patent number
US07368424B2

Reaction notes

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