Chloroacetic Acid → [2-[(Tetrahydropyran-2-yl)thio]ethoxy]acetic acid

HRID 275286Notes

Reaction equation

HRID 275286 reaction equation
Cl[CH2:2][C:3]([OH:5])=[O:4].C([Li])CCC.[O:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH:12]1[S:17][CH2:18][CH2:19][OH:20]>O1CCCC1.CN1C(=O)N(C)CCC1.CCCCCC.O1CCCC1>[O:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH:12]1[S:17][CH2:18][CH2:19][O:20][CH2:2][C:3]([OH:5])=[O:4]

Participants

7

Reactant 3

HCID 300Chloroacetic AcidHCID 152383212-[(Tetrahydropyran-2-yl)thio]ethanolHCID 178418339Butyllithium2×

Product 1

HCID 15238322[2-[(Tetrahydropyran-2-yl)thio]ethoxy]acetic acidYield 51.1%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent2×HCID 22565281tetrahydrofuran 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinoneSolvent

Procedure

To a solution of chloroacetic acid (22.7 g) in tetrahydrofuran-DMPU (5:1, 300 ml) was added a solution of butyllithium (0.24 mol) in hexane (150 ml) at -78° C. and the resulting suspension was warmed to room temperature. Separately, a solution of butyllithium (0.24 mol) in hexane (150 ml) was added to a solution of 2-[(tetrahydropyran-2-yl)thio]ethanol (38.9 g) in tetrahydrofuran (200 ml) at -78° C. and this solution was also warmed to room temperature. This solution and the above suspension were pooled and refluxed for 18 hours. After cooling, the reaction mixture was diluted with ice-aqueous sodium chloride solution (water-saturated NaCl solution=3:1, 400 ml) and the unreacted chloroacetic acid was extracted with ether (200 ml×6). The aqueous layer was adjusted to pH 2 with 4N-hydrochloric acid and extracted with ether (200 ml×3). The organic layer was washed successively with aqueous sodium chloride solution (saturated aqueous sodium chloride solution-water=1:1, 200 ml×2) and saturated aqueous sodium chloride solution (100 ml) and dried over anhydrous sodium sulfate. Finally the solvent was distilled off under reduced pressure to give 27.0 g of [2-[(tetrahydropyran-2-yl)thio]ethoxy]acetic acid as a colorless oil.

Workup

  1. temperaturethis solution was also warmed to room temperature
  2. temperaturerefluxed for 18 hours
  3. temperatureAfter cooling
  4. extractionthe unreacted chloroacetic acid was extracted with ether (200 ml×6)
  5. extractionextracted with ether (200 ml×3)
  6. washThe organic layer was washed successively with aqueous sodium chloride solution (saturated aqueous sodium chloride solution-water=1:1, 200 ml×2) and saturated aqueous sodium chloride solution (100 ml)
  7. dry with materialdried over anhydrous sodium sulfate
  8. distillationFinally the solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-22f6858efcb9433595fc404dbf1d7abd
Source dataset
uspto-grants-1995_02
Patent number
US05393751

Reaction notes

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