2,6-Lutidine → HCID 59371458, compound

HRID 2095363Notes

Reaction equation

HRID 2095363 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[C:16]([CH2:20][CH2:21][C:22]2[CH:23]=[C:24]([CH2:28]O)[CH:25]=[CH:26][CH:27]=2)[CH:17]=[N:18][CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].[Cl-].N1C(C)=CC=CC=1C.CS([Cl:44])(=O)=O.S([O-])(=O)(=O)C>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[C:16]([CH2:20][CH2:21][C:22]2[CH:23]=[C:24]([CH2:28][Cl:44])[CH:25]=[CH:26][CH:27]=2)[CH:17]=[N:18][CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 79372,6-LutidineHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 433294Lithium ChlorideHCID 59371507HCID 59371507, compound

Product 1

HCID 59371458HCID 59371458, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-[2-[5-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]ethyl]phenylmethanol, LiCl (1-4 equiv.), and 2,6-lutidine (1-2 equiv.) in DMF is added with stirring, cooling, and exclusion of moisture methanesulfonyl chloride (1-1.5 equiv.). The reaction mixture is stirred at ambient or elevated temperature until the alcohol and the intermediate mesylate have disappeared. The solvent is then distilled into a cooled receiver in an oil pump vacuum. The residue is diluted with EtOAc and aqueous NaHCO3 solution. The phases are separated. The organic phase is washed with brine, dried over MgSO4, and evaporated, and the residue is used directly in the subsequent step. A purer product is obtained by filtration over silica gel with EtOAc or a mixture of EtOAc with a nonpolar solvent. The product is not stable in storage and should be carried forward promptly.

Workup

  1. temperaturecooling
  2. distillationThe solvent is then distilled into a cooled receiver in an oil pump vacuum
  3. additionThe residue is diluted with EtOAc and aqueous NaHCO3 solution
  4. customThe phases are separated
  5. washThe organic phase is washed with brine
  6. dry with materialdried over MgSO4
  7. customevaporated
  8. customA purer product is obtained by filtration over silica gel with EtOAc

Sources & evidence

ORD record
ord-129364070e324feca38245fbed9c2189
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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