1,2-Dichloroethane → methyl (2S)-2-{[(tert-butoxy)carbonyl]amino}-3-(pyridin-3-yl)propanoate

HRID 2237379Notes

Reaction equation

HRID 2237379 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:17]([OH:19])=[O:18])[CH2:10][C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CO.[CH2:22](Cl)CCl>ClCCl.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:17]([O:19][CH3:22])=[O:18])[CH2:10][C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 887MethanolHCID 7020919Boc-3-(3-pyridyl)-Ala-OH

Product 1

HCID 15337847methyl (2S)-2-{[(tert-butoxy)carbonyl]amino}-3-(pyridin-3-yl)propanoate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(2S)—N-(tert-Butoxycarbonyl)-3-(pyridin-3-yl)alanine (25.00 g, 93.88 mmol) is dissolved in 300 ml of dichloromethane under argon. Methanol (11.4 ml, 9.02 g, 281 mmol, 3 equivalents) and one grain of DMAP are added. The mixture is then cooled to 0° C. EDC (19.80 g, 103 mmol, 1.1 equivalents) is added. After 5 min, the ice bath is removed and the mixture is left to stir at RT over 1 h. The mixture is then concentrated in vacuo, and ethyl acetate is added to the residue and the mixture is extracted against a saturated sodium hydrogen carbonate solution. The aqueous phase is reextracted once with ethyl acetate, then the combined organic phases are washed with 0.5 M citric acid and then once again with a saturated sodium hydrogen carbonate solution. The organic phase is dried over sodium sulfate, filtered and concentrated in vacuo. An oil remains, which crystallizes during drying in an oil-pump vacuum. Yield: 23.60 g (90% of theory).

Workup

  1. customthe ice bath is removed
  2. waitthe mixture is left
  3. concentrationThe mixture is then concentrated in vacuo, and ethyl acetate
  4. additionis added to the residue
  5. extractionthe mixture is extracted against a saturated sodium hydrogen carbonate solution
  6. washthe combined organic phases are washed with 0.5 M citric acid
  7. dry with materialThe organic phase is dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customwhich crystallizes
  11. customduring drying in an oil-pump vacuum

Sources & evidence

ORD record
ord-c4d2033772474d598f1035de413b6ebd
Source dataset
uspto-grants-2010_05
Patent number
US07718611B2

Reaction notes

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