Tributyltin azide → 3-Tetrazolyl-2-(1,1-dimethylethoxy)methanamidopropionic acid

HRID 861571Notes

Reaction equation

HRID 861571 reaction equation
[C:1]([CH2:3][CH:4]([NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C:5]([OH:7])=[O:6])#[N:2].C([Sn]([N:29]=[N+:30]=[N-:31])(CCCC)CCCC)CCC>O1CCCC1>[NH:29]1[C:1]([CH2:3][CH:4]([NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C:5]([OH:7])=[O:6])=[N:2][N:31]=[N:30]1

Participants

4

Reactant 2

HCID 4984872Tributyltin azideHCID 14585624Alanine, 3-cyano-N-[(1,1-dimethylethoxy)carbonyl]- (9CI)

Product 1

HCID 1784533493-Tetrazolyl-2-(1,1-dimethylethoxy)methanamidopropionic acidYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

17.5 g (82 mmol, 1 equiv.) of 3-cyano-2-(1,1-dimethylethoxy) methanamido-propionic acid 26 was dissolved in 125 mL of tetrahydrofuran and 40.5 g (129 mmol, 1.5 equiv.) tributyltin azide was added. The reaction mixture was brought to reflux and held there for 3 days. The reaction mixture was cooled and the volatiles removed in vacuo on a rotary evaporator. The residue was dissolved in 300 mL of 0.5M sodium hydroxide and this aqueous solution was washed with ethyl acetate (4×100 mL). The aqueous layer was passed through a 125 mL bed of Dowex 50X8-400 ion exchange resin and the resin washed with four column volumes of 1:1 methanol:water. The volatiles were removed in vacuo on the rotary evaporator to yield 17.9 g of the product as a white solid (85 % yield). 1H-NMR (CD3OD): 4.55 p.p.m (m, 1H); 3.40 p.p.m. (m, 2H); 1.40 p.p.m. (s, 9H). This material is suitable for use in solid-phase peptide synthesis.

Workup

  1. temperatureto reflux
  2. temperatureThe reaction mixture was cooled
  3. customthe volatiles removed in vacuo on a rotary evaporator
  4. dissolutionThe residue was dissolved in 300 mL of 0.5M sodium hydroxide
  5. washthis aqueous solution was washed with ethyl acetate (4×100 mL)
  6. washthe resin washed with four column volumes of 1:1 methanol
  7. customThe volatiles were removed in vacuo on the rotary evaporator

Sources & evidence

ORD record
ord-7d195a2eef0640d0ace2e1594ee8f9a9
Source dataset
uspto-grants-1998_02
Patent number
US05714580

Reaction notes

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