Ethyl chloroformate → Ethyl [5-[5-phenylethynylthiazol-2-yl]thien-2-yl]carboxylate

HRID 2232389Notes

Reaction equation

HRID 2232389 reaction equation
[C:1]1([C:7]#[C:8][C:9]2[S:13][C:12]([C:14]3[S:15][CH:16]=[CH:17][CH:18]=3)=[N:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])CCC.Cl[C:25]([O:27][CH2:28][CH3:29])=[O:26].[Cl-].[NH4+]>O1CCCC1.CCCCCC>[C:1]1([C:7]#[C:8][C:9]2[S:13][C:12]([C:14]3[S:15][C:16]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:17][CH:18]=3)=[N:11][CH:10]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 10928Ethyl chloroformateHCID 25517Ammonium ChlorideHCID 14405340HCID 14405340, compoundHCID 178418339Butyllithium

Product 1

HCID 14405348Ethyl [5-[5-phenylethynylthiazol-2-yl]thien-2-yl]carboxylateYield 80.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

Under a dry nitrogen atmosphere, a stirred solution of 0.80 gram (0.0030 mole) of 1-phenyl-2-[2-(thien-2-yl)thiazol-5-yl]ethyne in 20 ml of tetrahydrofuran was cooled to -78° C. A solution of n-butyllithium (1.4 ml of a 2.1M solution in hexane) was added, and the mixture was stirred at -78° C. for two hours. This mixture was transferred to another reaction flask containing a stirred solution of 0.65 gram (0.0060 mole) of ethyl chloroformate in 10 ml of tetrahydrofuran. This reaction mixture was allowed to warm slowly to room temperature and stir for approximately 18 hours. An aqueous, saturated ammonium chloride solution (20 ml) was added dropwise. The resultant mixture was extracted with diethyl ether. The organic extract was washed with water followed by an aqueous, saturated sodium chloride solution. The washed extract was dried over anhydrous sodium sulfate and was filtered. The filtrate was evaporated under reduced pressure leaving a residue. This residue was purified by column chromatography on silica gel, eluting with methylene chloride:n-hexane (3:2), to yield 0.82 gram of ethyl [5-[5-phenylethynylthiazol-2-yl]thien-2-yl]carboxylate as a solid, m.p. 137°-141° C., Compound 30 of Table 1.

Workup

  1. customThis mixture was transferred to another reaction flask
  2. temperatureto warm slowly to room temperature
  3. stirringstir for approximately 18 hours
  4. extractionThe resultant mixture was extracted with diethyl ether
  5. extractionThe organic extract
  6. washwas washed with water
  7. extractionThe washed extract
  8. dry with materialwas dried over anhydrous sodium sulfate
  9. filtrationwas filtered
  10. customThe filtrate was evaporated under reduced pressure
  11. customleaving a residue
  12. customThis residue was purified by column chromatography on silica gel
  13. washeluting with methylene chloride:n-hexane (3:2)

Sources & evidence

ORD record
ord-1e86985f3d4d4c2f8bb2b8cb10c15510
Source dataset
uspto-grants-1988_11
Patent number
US04788207

Reaction notes

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