Thiazole → HCID 19797824, compound

HRID 1722572Notes

Reaction equation

HRID 1722572 reaction equation
S1C=CN=C1.Cl.[OH:7]/[N:8]=[C:9](/[C:15]1[N:16]=[C:17]([NH:20][C:21]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[S:18][CH:19]=1)\[C:10]([O:12]CC)=[O:11].C(=O)([O-])[O-].[K+].[K+].[CH2:46]([O:48][CH2:49][CH2:50]Br)[CH3:47]>CN(C=O)C.O>[CH2:46]([O:48][CH2:49][CH2:50][O:7]/[N:8]=[C:9](/[C:15]1[N:16]=[C:17]([NH:20][C:21]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[S:18][CH:19]=1)\[C:10]([OH:12])=[O:11])[CH3:47]

Participants

7

Reactant 4

HCID 9256ThiazoleHCID 11430Potassium CarbonateHCID 611412-Bromoethyl ethyl etherHCID 9589415(Z)-Ethyl 2-(hydroxyimino)-2-(2-(tritylamino)thiazol-4-yl)acetate hydrochloride

Product 1

HCID 19797824HCID 19797824, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

The thiazole acid starting material was prepared as follows. Ethyl (Z)-2-hydroxyimino-2-(2-tritylaminothiazol-4-yl)acetate hydrochloride (9.87 g.) was suspended in DMF (50 ml.) and treated with potassium carbonate (5.52 g.) and 2-bromoethyl ethyl ether (2.25 ml.). After stirring for 10 days at ambient temperature the mixture was diluted with water and worked up conventionally by extraction into EtOAc followed by chromatography on silica, eluting with 98:2 (v/v) CH2Cl2 : EtOAc. The ethyl ester was dissolved in 1,2-dimethoxyethane (12 ml.), 2N aqueous NaOH solution (8.9 ml.) added, and the mixture heated under reflux for 2 hours. The mixture was cooled to 0°, the precipitate filtered, washed with a mixture of dimethoxyethane/water (1:1, v/v, 2×10 ml.) then dimethoxyethane/ether (1:1, v/v, 10 ml.). The precipitate was suspended in DMSO (50 ml.), acidified with 2NHCl (10 ml.), and diluted with water (500 ml.). The precipitate was filtered, washed well with water, and dried to give 2-((Z)-2-ethoxyethoxyimino)-2-(2-tritylaminothiazol-4-yl)acetic acid, having the following n.m.r. in CDCl3 :-1.07(t, 3H); 3.43(q, 2H); 3.62(t, 2H); 4.23(t, 2H); 6.5(s, 1H); 7.27(s, 15H).

Workup

  1. customwas prepared
  2. extractionworked up conventionally by extraction into EtOAc
  3. washeluting with 98:2 (v/v) CH2Cl2
  4. dissolutionThe ethyl ester was dissolved in 1,2-dimethoxyethane (12 ml.)
  5. addition2N aqueous NaOH solution (8.9 ml.) added
  6. temperaturethe mixture heated
  7. temperatureunder reflux for 2 hours
  8. temperatureThe mixture was cooled to 0°
  9. filtrationthe precipitate filtered
  10. washwashed with a mixture of dimethoxyethane/water (1:1, v/v, 2×10 ml.)
  11. additiondiluted with water (500 ml.)
  12. filtrationThe precipitate was filtered
  13. washwashed well with water
  14. customdried

Sources & evidence

ORD record
ord-2ce6d5bbea9a4951af86f89db21bf39f
Source dataset
uspto-grants-1989_08
Patent number
US04855420

Reaction notes

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