3-Pyridinemethanol → HCID 15344102, compound

HRID 1077581Notes

Reaction equation

HRID 1077581 reaction equation
OCC1C=NC=CC=1.C(N(CC)CC)C.[CH3:16][S:17](Cl)(=[O:19])=[O:18].Cl.COC([C@@H]1C[C@@H](O)CN1)=O.[N:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38][N:39]2[CH2:43][C@H:42]([OH:44])[CH2:41][C@H:40]2[C:45]([O:47][CH3:48])=[O:46])[CH:33]=1>CN(C)C=O.O.C(OCC)(=O)C>[N:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38][N:39]2[CH2:43][C@H:42]([O:44][S:17]([CH3:16])(=[O:19])=[O:18])[CH2:41][C@H:40]2[C:45]([O:47][CH3:48])=[O:46])[CH:33]=1

Participants

9

Reactant 5

HCID 75103-PyridinemethanolHCID 8471Triethylamine3×HCID 31297Methanesulfonyl chloride2×HCID 114353194-Hydroxy-L-proline methyl ester hydrochlorideHCID 57030131HCID 57030131, compound

Product 1

HCID 15344102HCID 15344102, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

In an atmosphere of nitrogen, 3-hydroxymethylpyridine (35.95 g, 0.329 mol) was dissolved in N,N-dimethylformamide (250 ml) followed by cooling to -15°~-20° C. Then, triethylamine (36.65 g, 0.329 mol) was added thereto and methanesulfonyl chloride (41.45 g, 0.362 mol) was added dropwise to the mixture at 0°~-10° C. After completion of the dropwise addition, the mixture was stirred at -10° C. for 30 minutes. To this mixture were added (2S,4R)-2-methoxycarbonyl-4-hydroxypyrrolidine hydrochloride (50 g, 0.275 mol) and triethylamine (100 g, 0.988 mol) followed by warming to 65° C. The mixture was stirred at 65° C. for 1 hour to provide a reaction mixture containing (2S,4R)-1-(3-pyridylmethyl)-2-methoxycarbonyl-4-hydroxypyrrolidine. This reaction mixture was cooled to -20° C. and triethylamine (66.8 g, 0.66 mol) was added thereto. Then, methanesulfonyl chloride (75.6 g, 0.66 mol) was added thereto dropwise at -20°~-15° C. The mixture was stirred at -20°~-25° C. for 1 hour, after which it was poured into ethyl acetate (1 l)-water (1 l) and extracted. After phase separation, the aqueous layer was extracted with ethyl acetate (500 ml) twice. The ethyl acetate layer was combined and washed with a saturated aqueous sodium chloride solution (125 ml). The ethyl acetate layer was concentrated to dryness under reduced pressure to provide (2S,4R)-1-(3-pyridylmethyl)-2-methoxycarbonyl-4-methylsulfonyloxypyrrolidine (84.65 g) as an oil.

Workup

  1. temperatureby cooling to -15°~-20° C
  2. additionAfter completion of the dropwise addition
  3. temperatureby warming to 65° C
  4. stirringThe mixture was stirred at 65° C. for 1 hour
  5. customto provide a reaction mixture
  6. temperatureThis reaction mixture was cooled to -20° C.
  7. customdropwise at -20°~-15° C
  8. stirringThe mixture was stirred at -20°~-25° C. for 1 hour
  9. extractionextracted
  10. customAfter phase separation
  11. extractionthe aqueous layer was extracted with ethyl acetate (500 ml) twice
  12. washwashed with a saturated aqueous sodium chloride solution (125 ml)
  13. concentrationThe ethyl acetate layer was concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-b4fafa224879427c94901a9fd089b091
Source dataset
uspto-grants-1996_08
Patent number
US05543525

Reaction notes

Loading…