Triethylamine → HCID 76083774, compound

HRID 2082612Notes

Reaction equation

HRID 2082612 reaction equation
[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24]([C:26](=[N:30][O:31][CH3:32])[C:27](O)=[O:28])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.ON1C2C=CC=CC=2N=N1.[CH3:50][C:51]([O:54][C:55]([C:57]1[N:58]2[CH:61]([S:62][CH2:63][C:64]=1[CH2:65][O:66][C:67](=[O:69])[CH3:68])[CH:60]([NH2:70])[C:59]2=[O:71])=[O:56])([CH3:53])[CH3:52]>ClCCl>[CH3:53][C:51]([O:54][C:55]([C:57]1[N:58]2[CH:61]([S:62][CH2:63][C:64]=1[CH2:65][O:66][C:67](=[O:69])[CH3:68])[CH:60]([NH:70][C:27](=[O:28])[C:26](=[N:30][O:31][CH3:32])[C:24]1[N:25]=[C:21]([NH:20][C:1]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[S:22][CH:23]=1)[C:59]2=[O:71])=[O:56])([CH3:50])[CH3:52]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 2724510(Z)-2-(2-Tritylaminothiazol-4-yl)-2-methoxyiminoacetic acidHCID 11771800HCID 11771800, compound

Product 1

HCID 76083774HCID 76083774, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred suspension of 48 g (0.1 mole) of 2-[2-(tritylamino)thiazole-4-yl]-2-methoxyiminoacetic acid in 750 mL of anhydrous dichloromethane was added 13.94 mL (0.1 mole) of triethylamine and the mixture was mechanically stirred until a clear solution formed (approx. 45 min). After complete dissolution 20.6 g (0.1 mole) of N,N-dicyclohexylcarbodiimide and 13.5 g (0.1 mole) of 1-hydroxybenzotriazole were added and the mixture stirred at ambient temperature for 2 hours. A solution of 32.8 g (0.1 mole) of [6R-[6 alpha,7 beta(z)]]-3-(acetoxymethyl)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2 carboxylic acid 1,1-dimethylethyl ester (from Example 1) in 250 mL of anhydrous dichloromethane was added and the resulting solution was stirred overnigh (16 hours) at ambient temperature. The precipitate was removed by filtration and the filtrate was washed successively with 2×250 mL=500 mL of saturated aqueous sodium bicarbonate and 2×250 mL=500 mL of saturated aqueous sodium chloride and dried over sodium sulphate. Removal of the dichloromethane afforded the crude product as a gummy-oil which was purified by preparative liquid chromatography (0-10% EtoAc in CH2Cl2), to give 57.2 g (76%) of pale yellow solid. NMR (CDCl3): 1.54 (s) 9H (t-bu) 2.09 (s) 3H (OAc); 3.35, 3.56 (d of d, J=18 Hz) 2H (CH2S); 4.08 (s) 3H (OCH3); 4.86 5.04 (d of d, J=14 Hz) 2H (CH2O); 5.04 (d, J=6 Hz) 1H (C6); 5.93 (d of d, J=6 Hz J=10 Hz), 1H (C7); 6.71 (s) 1H (thiazole); 6.91 (d, J=10 Hz) 1H (NH); 7.08 (s) 1H (NH); 7.30 (s) 15H (CPh3).

Workup

  1. customformed (approx. 45 min)
  2. additionwere added
  3. stirringthe mixture stirred at ambient temperature for 2 hours
  4. stirringthe resulting solution was stirred overnigh (16 hours) at ambient temperature
  5. customThe precipitate was removed by filtration
  6. washthe filtrate was washed successively with 2×250 mL=500 mL of saturated aqueous sodium bicarbonate and 2×250 mL=500 mL of saturated aqueous sodium chloride
  7. dry with materialdried over sodium sulphate
  8. customRemoval of the dichloromethane
  9. customafforded the crude product as a gummy-oil which
  10. customwas purified by preparative liquid chromatography (0-10% EtoAc in CH2Cl2)

Sources & evidence

ORD record
ord-8e9f44a614bb4d3892ca21f9b168d046
Source dataset
uspto-grants-1993_02
Patent number
US05189157

Reaction notes

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