Water → HCID 21249058, compound

HRID 1194944Notes

Reaction equation

HRID 1194944 reaction equation
S(Cl)([O:4][CH2:5][Cl:6])(=O)=O.[N+:8]([C:11]1[CH:34]=[CH:33][C:14]([CH2:15][O:16][C:17]([NH:19][CH2:20][C:21]([NH:23][C:24]2[CH:32]=[CH:31][CH:30]=[CH:29][C:25]=2[C:26](O)=[O:27])=[O:22])=[O:18])=[CH:13][CH:12]=1)([O-:10])=[O:9].C(=O)(O)[O-].[Na+].O>ClCCl.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[N+:8]([C:11]1[CH:34]=[CH:33][C:14]([CH2:15][O:16][C:17]([NH:19][CH2:20][C:21]([NH:23][C:24]2[CH:32]=[CH:31][CH:30]=[CH:29][C:25]=2[C:26]([O:4][CH2:5][Cl:6])=[O:27])=[O:22])=[O:18])=[CH:13][CH:12]=1)([O-:10])=[O:9]

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 2733556Chloromethyl chlorosulfateHCID 21248844HCID 21248844, compound

Product 1

HCID 21249058HCID 21249058, compound

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A solution of chloromethyl chlorosulphate (275 mg) in dichloromethane (1 ml) was added, dropwise over 1/2 minute, to a stirred mixture of 2-[N-(4-nitrobenzyloxycarbonyl)glycylamino]benzoic acid (500 mg), sodium bicarbonate (450 mg), tetrabutylammonium hydrogensulphate (70 mg), dichloromethane (10 ml), and water (10 ml). After stirring at room temperature for 1h the solid which had precipitated was redissolved by addition of dichloromethane (50 ml). The organic layer was separated and was washed with dilute brine (2×10 ml), dried (MgSO4), and evaporated to give the crude product, chloromethyl 2-[N-(4-nitrobenzyloxycarbonyl)glycylamino]benzoate, as a solid. Without further purification, the crude chloromethyl ester was dissolved in dry acetone (50 ml) and was treated with sodium iodide (2.11 g). After stirring at room temperature for 24 h the mixture was evaporated. The residue was dissolved in ethyl acetate (50 ml) and was washed with water (3×10 ml), dried (MgSO4), and evaporated to give the crude product, iodomethyl 2 -[N-(4-nitrobenzyloxycarbonyl)glycylamino]benzoate, as a solid. Without futher purification, the crude iodomethyl ester was dissolved in dry dimethylformamide (10 ml) and treated with sodium 6β-[2-(2-aminothiazol-4-yl)-(Z)-2-(cyclohexyloxyimino)a cetamido]penicillanate (688 mg). After stirring at room temperature for 1 h the mixture was diluted with ethyl acetate (50 ml) and was washed with 5% citric acid (10 ml), brine (10 ml), saturated NaHCO3 (10 ml), and brine (3×10 ml). The dried (MgSO4) organic layer was evaporated and the residue chromatographed on silica gel eluting with methyl acetate/hexane mixtures to give the title compound as an amorphous solid (550 mg), νmax (CHCl3) 3600-3100, 1790, 1730 sh., and 1695 cm-1 ; δH [(CD3)2CO] 1.20-2.00 (16H, m), 4.03 (2H, d, J 6.3 Hz, collapses to s on exch. D2O), 4.05-4.25 (1H, m), 4.50 (1H, s), 5.36 (2H, s), 5.68 (1H, d, J 4.2 Hz), 5.7.9 (1H, dd, J 8.3 and 4.2 Hz, collapses to d, J 4.2 Hz on exch. D2O), 6.12 and 6.17 (2H, AB q, J 6.0 Hz), 6.55 (2H, s, exch. D2O), 6.83 (1H, s), 7.18-7.40 (2H, m, IH exch. D2O), 7.65-7.72 (1H, m), 7.76 (2H, d, J 8.4 Hz), 8.07 (1H, d, J 8.0 Hz), 8.12 (1H, d, J 8.3 Hz, exch. D2O), 8.27 (2H, d, J 8.4 Hz), 8.76 (1H, d, J 8.4 Hz), and 11.27 (1H, s, exch. D2O).

Workup

  1. customhad precipitated
  2. dissolutionwas redissolved by addition of dichloromethane (50 ml)
  3. customThe organic layer was separated
  4. washwas washed with dilute brine (2×10 ml)
  5. dry with materialdried (MgSO4)
  6. customevaporated

Sources & evidence

ORD record
ord-6e5a1546115d4ce4b9b0de25cef79113
Source dataset
uspto-grants-1989_03
Patent number
US04816452

Reaction notes

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