Hydrochloric Acid → Tert-butyl 3-hydroxy-3-phenyl-3-(pyridin-2-yl)propionate

HRID 7218Notes

Reaction equation

HRID 7218 reaction equation
C=C[C@@H]1[C@@H:8]2[CH2:9][C@H:10]([C@@H:11]([OH:22])[C:12]3[CH:13]=[CH:14]N=C4C=C[CH:19]=[CH:18][C:17]=34)[N:5]([CH2:6][CH2:7]2)C1.N1C=CC=C[CH:24]=1.[C:29]([C:37]1C=CC=CN=1)(=[O:36])[C:30]1C=CC=CC=1.Cl.[O:44]1CC[CH2:46][CH2:45]1>>[OH:22][C:11]([C:12]1[CH:17]=[CH:18][CH:19]=[CH:14][CH:13]=1)([C:10]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1)[CH2:46][C:45]([O:36][C:29]([CH3:30])([CH3:37])[CH3:24])=[O:44]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 70382-BenzoylpyridineHCID 8028Tetrahydrofuran2×HCID 90454Cinchonine

Product 1

HCID 12150309Tert-butyl 3-hydroxy-3-phenyl-3-(pyridin-2-yl)propionateYield 98%

Conditions

Temperature
-40 °C

Procedure

Under argon atmosphere, cinchonine (440 mg, 1.0 mmol) was suspended in tetrahydrofuran (absolute, 2.0 mL), and to this suspension was added a Reformatsky reagent (0.5 M; 8.0 mL, 4.0 mmol) dropwise under ice-cooling. After stirring for 10 minutes, pyridine (0.30 mL, 2 mmol) was added thereto dropwise. After stirring for 20 minutes under ice-cooling, the mixture was cooled to −40° C. A solution of 2-benzoylpyridine (183 mg, 1.0 mmol) in tetrahydrofuran (absolute, 4.0 mL) was added dropwise over 10 minutes, and the mixture was stirred at −40° C. for 4 hours. To this reaction solution was added 1N HCl (20 mL), which was then extracted with ethyl acetate (20 mL×2). The extracted solution was washed successively with an aqueous saturated sodium bicarbonate solution and an aqueous saturated sodium chloride solution. After the organic layer was dried with sodium sulfate, the solvent was removed under reduced pressure. The residue was analyzed with high performance liquid chromatography. Consequently, the yield was 98% and the enantiomer excess was 90%.

Workup

  1. additionto this suspension was added a Reformatsky reagent (0.5 M; 8.0 mL, 4.0 mmol) dropwise under ice-
  2. temperaturecooling
  3. stirringAfter stirring for 20 minutes under ice-
  4. temperaturecooling
  5. stirringthe mixture was stirred at −40° C. for 4 hours
  6. extractionwas then extracted with ethyl acetate (20 mL×2)
  7. washThe extracted solution was washed successively with an aqueous saturated sodium bicarbonate solution
  8. dry with materialAfter the organic layer was dried with sodium sulfate
  9. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-83ed61dbe4a343a899a0eeb5417de98f
Source dataset
uspto-grants-2006_08
Patent number
US07084278B2

Reaction notes

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