Benzyl Alcohol → HCID 89444402, compound

HRID 525994Notes

Reaction equation

HRID 525994 reaction equation
[C:1]1([CH2:7][OH:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)(Cl)=O.[O:13]=[C:14]([NH:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][N:22]=1)[CH2:15][CH2:16][C:17](O)=[O:18]>>[O:13]=[C:14]([NH:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:28])[F:29])=[CH:23][N:22]=1)[CH2:15][CH2:16][C:17]([O:8][CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:18]

Participants

4

Reactant 3

HCID 244Benzyl AlcoholHCID 24386Thionyl ChlorideHCID 84352846HCID 84352846, compound

Product 1

HCID 89444402HCID 89444402, compound

Procedure

To a solution of phenylmethanol (3 mL) was added dropwise thionyl chloride (3 equiv., 2.29 mmol, 0.169 mL). After 5 min, 4-oxo-4-[[5-(trifluoromethyl)-2-pyridyl]amino]butanoic acid A19 (prepared as described before, 201 mg, 0.766 mmol) was added to the solution. The reaction mixture was stirred overnight at room temperature. The reaction was stopped and the solution was partitioned between ethyl acetate and a saturated solution of sodium hydrogenocarbonate. The aqueous layer was separated and extracted with ethyl acetate (2×). The combined organic layer was washed with water (×2) and brine, dried on magnesium sulfate and concentrated under vacuum. To remove the benzyl alcohol, water was added until the ester precipitated. The ester was filtrated and then washed with water and cyclohexane (20 mL). The residue was first dissolved in ethyl acetate then precipitated with cyclohexane and the solid obtained was filtered to give benzyl 4-oxo-4-[[5-(trifluoromethyl)-2-pyridyl]amino]butanoate A34 (32%). 1H NMR (400 MHz, CDCl3) 8.7 (s, 1H), 8.31 (m, 1H), 8.22 (bs, 1H), 7.90 (m, 1H), 7.35 (m, 5H), 5.15 (s, 2H), 2.78 (m, 4H) ppm. Compound A51, A52, A53, A54, A73, A74, A78, A79, A80 and A81 from table A were prepared by the same method using the corresponding alcohol.

Workup

  1. additionwas added to the solution
  2. customthe solution was partitioned between ethyl acetate
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (2×)
  5. washThe combined organic layer was washed with water (×2) and brine
  6. customdried on magnesium sulfate
  7. concentrationconcentrated under vacuum
  8. customTo remove the benzyl alcohol, water
  9. additionwas added until the ester
  10. customprecipitated
  11. filtrationThe ester was filtrated
  12. washwashed with water and cyclohexane (20 mL)
  13. dissolutionThe residue was first dissolved in ethyl acetate
  14. customthen precipitated with cyclohexane
  15. customthe solid obtained
  16. filtrationwas filtered

Sources & evidence

ORD record
ord-2702256a60a84462ba469eb74df1622d
Source dataset
uspto-grants-2016_05
Patent number
US09345244B2

Reaction notes

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