Sodium Bicarbonate → HCID 59211952, compound

HRID 655190Notes

Reaction equation

HRID 655190 reaction equation
[C:1]([CH2:4][N:5]([CH2:19][C:20]([OH:22])=O)[C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:8][CH:7]=1)([OH:3])=[O:2].C(=O)(O)[O-].[Na+].[C:28]([O:32][C:33]([NH:35][C@H:36]1[CH2:40][CH2:39][NH:38][CH2:37]1)=[O:34])([CH3:31])([CH3:30])[CH3:29]>C(OC(=O)C)(=O)C>[C:28]([O:32][C:33]([NH:35][C@H:36]1[CH2:40][CH2:39][N:38]([C:20](=[O:22])[CH2:19][N:5]([CH2:4][C:1]([OH:3])=[O:2])[C:6]2[CH:7]=[CH:8][C:9]([O:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[CH:10][CH:11]=2)[CH2:37]1)=[O:34])([CH3:31])([CH3:29])[CH3:30]

Participants

5

Reactant 3

HCID 516892Sodium Bicarbonate2×HCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 59212042HCID 59212042, compound

Product 1

HCID 59211952HCID 59211952, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent

Procedure

A mixture of [carboxymethyl-(4-phenoxyphenyl)amino]acetic acid 19 (0.5 g, 1.66 mmol) in acetic anhydride (10 mL) was heated to reflux with stirring for 45 minutes. The reaction mixture was cooled to room temperature and poured into saturated aqueous sodium bicarbonate. Solid sodium bicarbonate was added and the mixture stirred until effervescence had ceased. The aqueous mixture was extracted with ethyl acetate (×2) and the organic fractions combined, washed with saturated aqueous sodium bicarbonate, brine, dried (Na2SO4) and evaporated to dryness. The residue was co-evaporated with toluene, dissolved in THF (10 mL) and added to (3S)-(−)-3-(tert-butoxycarbonylamino)pyrrolidine (0.39 g, 2.09 mmol). The reaction mixture was stirred for 3 days and then concentrated in vacuo. The residue was diluted with ethyl acetate and washed with 10% hydrochloric acid (×2), brine, dried (Na2SO4) and evaporated to dryness. The crude product was crystallized from ethyl acetate to give the title compound as a cream powder (0.35 g, 45%). 1HNMR (300 MHz) (CDCl3) δ 1.45 (6H, s), 1.55 (3H, s), 1.8-2.4 (2H, m), 3.4-3.9 (5H, m), 4.05-4.75 (4H, m), 6.48 (2H, m), 6.90-7.07 (5H, m) and 7.28 (2H, t).

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. stirringthe mixture stirred until effervescence
  4. extractionThe aqueous mixture was extracted with ethyl acetate (×2)
  5. washwashed with saturated aqueous sodium bicarbonate, brine
  6. dry with materialdried (Na2SO4)
  7. customevaporated to dryness
  8. dissolutiondissolved in THF (10 mL)
  9. stirringThe reaction mixture was stirred for 3 days
  10. concentrationconcentrated in vacuo
  11. additionThe residue was diluted with ethyl acetate
  12. washwashed with 10% hydrochloric acid (×2), brine
  13. dry with materialdried (Na2SO4)
  14. customevaporated to dryness
  15. customThe crude product was crystallized from ethyl acetate

Sources & evidence

ORD record
ord-cade8342b9034c7e95da9063dfd59825
Source dataset
uspto-grants-2011_12
Patent number
US08071582B2

Reaction notes

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