Triethylamine → Methyl 5-chloro-2-(3-hydroxyazetidin-1-yl)nicotinate

HRID 72429

Reaction equation

HRID 72429 reaction equation
Cl.[OH:2][CH:3]1[CH2:6][NH:5][CH2:4]1.C(N(CC)CC)C.Cl[C:15]1[N:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:16]=1[C:17]([O:19][CH3:20])=[O:18]>O1CCCC1.CO>[Cl:25][C:22]1[CH:23]=[N:24][C:15]([N:5]2[CH2:6][CH:3]([OH:2])[CH2:4]2)=[C:16]([CH:21]=1)[C:17]([O:19][CH3:20])=[O:18]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 27592903-Hydroxyazetidine hydrochloride2×HCID 2764318Methyl 2,5-Dichloronicotinate

Product 1

HCID 67958303Methyl 5-chloro-2-(3-hydroxyazetidin-1-yl)nicotinateYield 76.6%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To a mixture of 3-Hydroxyazetidine hydrochloride (37.17 g, 0.339 mol) and triethylamine (70.93 ml, 0.508 mol) in tetrahydrofuran/methanol (840/280 ml) Methyl 2,5-dichloronicotinate (70 g, 0.339 mol) was added and the resulting mixture was heated at 75° C. for 4 hours then at 62° C. overnight. 3-Hydroxyazetidine hydrochloride (3.7 g, 0.03 mol) and triethylamine (23.60 ml, 0.16 mol) were added and the reaction mixture was further heated at 80° C. for 28 h. Solvents were evaporated in vacuo. The residue was taken in dichloromethane (400 ml) and water (500 ml). The formed solid was filtered, washed with water (500 ml) and dried in vacuum to afford a first batch of the title compound (D62) (63 g).

Workup

  1. additionwas added
  2. customat 62° C.
  3. customovernight
  4. temperaturethe reaction mixture was further heated at 80° C. for 28 h
  5. customSolvents were evaporated in vacuo
  6. filtrationThe formed solid was filtered
  7. washwashed with water (500 ml)
  8. customdried in vacuum

Sources & evidence

ORD record
ord-25e4a4f6a52f415abe7623234769fe0c
Source dataset
uspto-grants-2014_09
Patent number
US08828987B2

Linked notes

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