Oxalyl chloride → Benzyl epsilon-(3-nitro-5-sulfobenzoylamino)caproate

HRID 1603192Notes

Reaction equation

HRID 1603192 reaction equation
[Na+].[N+:2]([C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([S:14]([OH:17])(=[O:16])=[O:15])[CH:13]=1)[C:8]([O-:10])=O)([O-:4])=[O:3].C(Cl)(=O)C(Cl)=O.[NH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31]>N1C=CC=CC=1.C1COCC1>[N+:2]([C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([S:14]([OH:17])(=[O:16])=[O:15])[CH:13]=1)[C:8]([NH:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])=[O:10])([O-:4])=[O:3]

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 3484395Benzyl 6-aminohexanoateHCID 883000033-Nitro-5-sulfobenzoic acid monosodium salt

Product 1

HCID 19609029Benzyl epsilon-(3-nitro-5-sulfobenzoylamino)caproateYield 35.2%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

14.6 g of 3-nitro-5-sulfobenzoic acid monosodium salt were dissolved in 300 ml of pyridine and stirred for 2 hours, after which 2.2 ml of oxalyl chloride were added dropwise. After 1 hour, 16.6 g of benzyl ε-aminocaproate as a solution in 100 ml of THF were added dropwise and the mixture was stirred overnight. The mixture was concentrated on a rotary evaporator and then stirred with 100 g of strongly acid ion exchanger in 100 ml water for 50 hours. The mixture was filtered and washed with water, and the filtrate was concentrated. The residue was dissolved in 30% methanol/water, treated with 21 g of tetraethylammonium bromide and adjusted to pH 6.5 with sodium hydroxide solution. The resulting solution was chromatographed on 500 g of silanized silica gel (RP2) with 30% methanol. 8.6 g of benzyl ε-(3-nitro-5-sulfobenzoylamino)caproate were obtained in the form of the tetraethylammonium salt, which was stirred with 100 g of cation exchanger in water, filtered off and washed with water. The filtrate was concentrated and gave the corresponding free sulfonic acid. TLC (silica gel: HOAc/EtOAc=20%) Rf=0.7 (educt=0.4); TLC (silica gel: NH3/EtOH=1%) Rf=0.8 (educt=0.7); TLC (RP18: EtOH/Et4N+ (0.01M) phosphate buffer (0.1M; pH 6.5)=60% Rf=0.4 (educt=0.8). HPLC (RP18: MeCN/Et4N+ (0.01M) phosphate buffer (0.1M; pH 6.5)=30%) tR =5.9 min. (educt=1.3 min). 1.32 g of benzyl 6-(3-nitro-5-sulfobenzoylamino)hexanoate were dissolved in 30 ml ethanol/water=60%, 100 mg of Pd/C 10% were added and the mixture was hydrogenated while stirring (magnetic stirrer). The total absorption of hydrogen (1.5 hours) was 235 ml. TLC control showed that starting material was no longer present. In the TLC the amine is present practically at the start. The catalyst was filtered off and the solution was concentrated to dryness on a rotary evaporator. The IR control of the substance showed the complete absence of the original nitro group and of the benzyl group. The resulting 6-(3-amino-5-sulfobenzoylamino)hexanoic acid was used directly for the preparation of the azide.

Workup

  1. waitAfter 1 hour
  2. stirringthe mixture was stirred overnight
  3. concentrationThe mixture was concentrated on a rotary evaporator
  4. stirringstirred with 100 g of strongly acid ion exchanger in 100 ml water for 50 hours
  5. filtrationThe mixture was filtered
  6. washwashed with water
  7. concentrationthe filtrate was concentrated
  8. dissolutionThe residue was dissolved in 30% methanol/water
  9. additiontreated with 21 g of tetraethylammonium bromide
  10. customThe resulting solution was chromatographed on 500 g of silanized silica gel (RP2) with 30% methanol

Sources & evidence

ORD record
ord-1aeee00b242a449c9fabcb3b5e372a60
Source dataset
uspto-grants-1999_11
Patent number
US05986066

Reaction notes

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