N-(tert-butoxycarbonyl)glycine → Ethyl 2-(2-(2-aminoacetamido)thiazol-4-yl)acetate

HRID 324402Notes

Reaction equation

HRID 324402 reaction equation
C(OC([NH:8][CH2:9][C:10](O)=[O:11])=O)(C)(C)C.[CH2:13]([O:15][C:16](=[O:24])[CH2:17][C:18]1[N:19]=[C:20]([NH2:23])[S:21][CH:22]=1)[CH3:14].F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.C(N(CC)C(C)C)(C)C>CN(C)C=O.CN(C)C1C=CN=CC=1>[CH2:13]([O:15][C:16](=[O:24])[CH2:17][C:18]1[N:19]=[C:20]([NH:23][C:10](=[O:11])[CH2:9][NH2:8])[S:21][CH:22]=1)[CH3:14]

Participants

7

Reactant 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 1044544-Thiazoleacetic acid, 2-amino-, ethyl esterHCID 2733179PyBroP

Product 1

HCID 54551034Ethyl 2-(2-(2-aminoacetamido)thiazol-4-yl)acetate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of N-(tert-butoxycarbonyl)glycine (3.1 g), 2-amino-4-thiazoleacetic acid ethyl ester (3 g) and bromo-tris(pyrrolidino)-phosphonium hexafluorophosphate (7.54 g) in N,N-dimethylformamide (20 ml) was treated with N,N-diisopropylethylamine (6 ml). After 25 minutes 4-(dimethylamino)pyridine (1.96 g) was added. After 24 hours the mixture was partitioned between ethyl acetate and brine. The organic phase was washed with saturated aqueous sodium bicarbonate, brine, 1N HCl and brine, dried (MgSO4) and evaporated. The residue was purified by chromatography eluting with 50% ethyl acetate in isohexane. The product (0.77 g) was dissolved in dichloromethane (25 ml) and trifluoroacetic acid (10 ml). After 2 hours the mixture was evaporated. The residue was partitioned between ethyl acetate and sodium bicarbonate solution. The aqueous phase was repeatedly extracted with ethyl acetate. The combined extracts were dried (MgSO4) and evaporated.

Workup

  1. customAfter 24 hours the mixture was partitioned between ethyl acetate and brine
  2. washThe organic phase was washed with saturated aqueous sodium bicarbonate, brine, 1N HCl and brine
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. customThe residue was purified by chromatography
  6. washeluting with 50% ethyl acetate in isohexane
  7. dissolutionThe product (0.77 g) was dissolved in dichloromethane (25 ml)
  8. customAfter 2 hours the mixture was evaporated
  9. customThe residue was partitioned between ethyl acetate and sodium bicarbonate solution
  10. extractionThe aqueous phase was repeatedly extracted with ethyl acetate
  11. dry with materialThe combined extracts were dried (MgSO4)
  12. customevaporated

Sources & evidence

ORD record
ord-f521315df6294a0086e2d68f7f5e32cd
Source dataset
uspto-grants-2001_04
Patent number
US06218376B1

Reaction notes

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