Dimethylformamide → Methyl 5-chloro-2-(3-((methylsulfonyl)oxy)azetidin-1-yl)nicotinate

HRID 72431

Reaction equation

HRID 72431 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:12]2[CH2:15][CH:14]([OH:16])[CH2:13]2)=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].C(N(CC)CC)C.CN(C)C=O.[CH3:29][S:30](Cl)(=[O:32])=[O:31]>>[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:12]2[CH2:13][CH:14]([O:16][S:30]([CH3:29])(=[O:32])=[O:31])[CH2:15]2)=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 8471Triethylamine2×HCID 31297Methanesulfonyl chlorideHCID 67958303Methyl 5-chloro-2-(3-hydroxyazetidin-1-yl)nicotinate

Product 1

HCID 86697874Methyl 5-chloro-2-(3-((methylsulfonyl)oxy)azetidin-1-yl)nicotinateYield 674.1%

Conditions

Temperature
0 °C

Procedure

To an ice cooled stirred solution of methyl 5-chloro-2-(3-hydroxyazetidin-1-yl)nicotinate (D62) (66 g, 0.27 mol) and triethylamine (56.86 ml, 0.40 mol) in dimethylformamide (500 ml) methanesulfonylchloride (23.15 ml, 0.29 mol) was added dropwise maintaining the temperature at 0° C. The reaction mixture was stirred at 0° C. for 3.5 h then methanesulfonyl chloride (6.3 ml, 0.037 mol) and triethylamine (18.9 ml, 0.135 mol) were added and the reaction mixture was stirred for 3 h at 0° C. After this time the formed solid was filtered off. Water (700 ml) was added to the filtrate. The formed solid was filtered off, washed with water (400 ml) and dried under vacuo to afford the title compound (D63) (80 g).

Workup

  1. additionwas added dropwise
  2. stirringthe reaction mixture was stirred for 3 h at 0° C
  3. filtrationAfter this time the formed solid was filtered off
  4. additionWater (700 ml) was added to the filtrate
  5. filtrationThe formed solid was filtered off
  6. washwashed with water (400 ml)
  7. customdried under vacuo

Sources & evidence

ORD record
ord-7a1a31ba7c184be0a9d3b2cfd6a2e82a
Source dataset
uspto-grants-2014_09
Patent number
US08828987B2

Linked notes

Loading…