3-Pyridinemethanol → HCID 15344102, compound

HRID 1488732Notes

Reaction equation

HRID 1488732 reaction equation
OCC1C=NC=CC=1.[CH3:9][S:10](Cl)(=[O:12])=[O:11].Cl.COC([C@@H]1C[C@@H](O)CN1)=O.[N:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH2:31][N:32]2[CH2:36][C@H:35]([OH:37])[CH2:34][C@H:33]2[C:38]([O:40][CH3:41])=[O:39])[CH:26]=1>CN(C)C=O.O.C(OCC)(=O)C.C(N(CC)CC)C>[N:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH2:31][N:32]2[CH2:36][C@H:35]([O:37][S:10]([CH3:9])(=[O:12])=[O:11])[CH2:34][C@H:33]2[C:38]([O:40][CH3:41])=[O:39])[CH:26]=1

Participants

9

Reactant 4

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

Product 1

HCID 15344102HCID 15344102, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent3×HCID 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, 0.98.8 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 gt 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-29683e8ef36d42779cb7f589cb598d7d
Source dataset
uspto-grants-1997_10
Patent number
US05675011

Reaction notes

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