Propargyl bromide → benzhydryl 7-(2-phenylacetamido)-3-[2-(2-propynyl)-2H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylate-1-oxide

HRID 1995789Notes

Reaction equation

HRID 1995789 reaction equation
[C:1]1([CH2:7][C:8]([NH:10][CH:11]2[C:42](=[O:43])[N:13]3[C:14]([C:26]([O:28][CH:29]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:27])=[C:15]([CH2:19][S:20][C:21]4[NH:25][N:24]=[N:23][N:22]=4)[CH2:16][S:17](=[O:18])[C@H:12]23)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:44](Br)[C:45]#[CH:46].C(N(CC)CC)C>CN(C)C=O>[C:1]1([CH2:7][C:8]([NH:10][CH:11]2[C:42](=[O:43])[N:13]3[C:14]([C:26]([O:28][CH:29]([C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=4)[C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)=[O:27])=[C:15]([CH2:19][S:20][C:21]4[N:22]=[N:23][N:24]([CH2:46][C:45]#[CH:44])[N:25]=4)[CH2:16][S:17](=[O:18])[C@H:12]23)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 7842Propargyl bromideHCID 8471TriethylamineHCID 178520244HCID 178520244, compound

Product 1

HCID 88675827benzhydryl 7-(2-phenylacetamido)-3-[2-(2-propynyl)-2H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylate-1-oxideYield 19.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of benzhydryl 7-(2-phenylacetamido)-3-(1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylate-1-oxide (78.0 g) in N,N-dimethylformamide (780 ml) was stirred to give a homogeneous solution and thereto were added 2-propynyl bromide (30.2 g) and triethylamine (38.5 g). The resulting solution was stirred for 22.3 hours at room temperature. The reaction mixture was added to ice-water (1.5 l) and the mixture was extracted with ethyl acetate (x 2). The extract was washed with water (x 4), dried over magnesium sulfate, treated with activated charcoal and then evaporated. The residue was pulverized in isopropyl ether, collected by filtration, washed with isopropyl ether and then dried. The obtained product (60.61 g) was subjected to column chromatography on silica gel (1.5 kg), using benzene and ethyl acetate (2:1) as an eluent. Fractions containing 2-(2-propynyl)-2H-tetrazolyl isomer, which were firstly eluted, were collected and then evaporated. The residue was pulverized in a mixture of isopropyl ether and n-hexane to give benzhydryl 7-(2-phenylacetamido)-3-[2-(2-propynyl)-2H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylate-1-oxide (16.34 g).

Workup

  1. customto give a homogeneous solution
  2. stirringThe resulting solution was stirred for 22.3 hours at room temperature
  3. extractionthe mixture was extracted with ethyl acetate (x 2)
  4. washThe extract was washed with water (x 4)
  5. dry with materialdried over magnesium sulfate
  6. additiontreated with activated charcoal
  7. customevaporated
  8. filtrationcollected by filtration
  9. washwashed with isopropyl ether
  10. customdried
  11. additionFractions containing 2-(2-propynyl)-2H-tetrazolyl isomer, which
  12. washwere firstly eluted
  13. customwere collected
  14. customevaporated
  15. additionThe residue was pulverized in a mixture of isopropyl ether and n-hexane

Sources & evidence

ORD record
ord-76d3b20410a14abaa4d2329423c237b0
Source dataset
uspto-grants-1983_09
Patent number
US04405617

Reaction notes

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