Acetic Acid → 2-(2-Trifluoromethyl-thiazol-4-yl)morpholine

HRID 477082Notes

Reaction equation

HRID 477082 reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]1[S:4][CH:5]=[C:6]([CH:8]2[O:13][CH2:12][C:11](=O)[NH:10][CH2:9]2)[N:7]=1.[BH4-].[Na+].C(O)(=O)C>O1CCCC1>[F:15][C:2]([F:1])([F:16])[C:3]1[S:4][CH:5]=[C:6]([CH:8]2[O:13][CH2:12][CH2:11][NH:10][CH2:9]2)[N:7]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 4311764Sodium borohydrideHCID 140762422-(2-Trifluoromethyl-thiazol-4-yl)morpholin-5-one

Product 1

HCID 199742652-(2-Trifluoromethyl-thiazol-4-yl)morpholine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 0.9 g (0.036 mol) of 2-(2-trifluoromethyl-thiazol-4-yl)morpholin-5-one in 40 ml of tetrahydrofuran at 3° C. is mixed with 1.35 g (0.036 mol) of sodium borohydride. Then, at 5°-8° C., very slowly and with vigorous stirring 2.43 g (0.036 mol) of glacial acetic acid dissolved in 20 ml of tetrahydrofuran are added dropwise. The cooling is removed after 2 hours, and the mixture is stirred at room temperature for 16 hours. After evaporation to dryness, the resulting residue is mixed with 15 ml of 20% strength hydrochloric acid, and the mixture is heated at 90° C. for 30 minutes. It is then evaporated to dryness, the resulting product is taken up in water, and the solution is made alkaline with sodium carbonate solution. The mixture is then extracted several times with methylene chloride, the organic phase is dried over sodium sulphate and concentrated, and the residue is purified on a silica gel column using ethyl acetate/methanol=8:2 as eluant.

Workup

  1. additionare added dropwise
  2. customThe cooling is removed after 2 hours
  3. customAfter evaporation to dryness
  4. additionthe resulting residue is mixed with 15 ml of 20% strength hydrochloric acid
  5. temperaturethe mixture is heated at 90° C. for 30 minutes
  6. customIt is then evaporated to dryness
  7. extractionThe mixture is then extracted several times with methylene chloride
  8. dry with materialthe organic phase is dried over sodium sulphate
  9. concentrationconcentrated
  10. customthe residue is purified on a silica gel column

Sources & evidence

ORD record
ord-f43fd102d20942c8add7410f6e89877e
Source dataset
uspto-grants-1989_12
Patent number
US04886814

Reaction notes

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