Azetidine → Ethyl 6-(azetidin-1-ylmethyl)-2-(trifluoromethyl)pyrimidine-4-carboxylate

HRID 1617405Notes

Reaction equation

HRID 1617405 reaction equation
[NH:1]1[CH2:4][CH2:3][CH2:2]1.Br[CH2:6][C:7]1[N:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[N:10]=[C:9]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:8]=1>C(Cl)Cl>[N:1]1([CH2:6][C:7]2[N:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[N:10]=[C:9]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:8]=2)[CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 10422Azetidine2×HCID 58431340Ethyl 6-(bromomethyl)-2-(trifluoromethyl)pyrimidine-4-carboxylate

Product 1

HCID 58431385Ethyl 6-(azetidin-1-ylmethyl)-2-(trifluoromethyl)pyrimidine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Azetidine (0.110 mL, 1.6 mmol, Aldrich) was added to a solution of ethyl 6-(bromomethyl)-2-(trifluoromethyl)pyrimidine-4-carboxylate (0.78 g, 1.1 mmol, prepared as in Example 376, Step A) in DCM (11 mL). After stirring for 20 minutes, additional azetidine (0.10 mL, 1 mmol) was added. After 10 minutes, excess reagents and solvent were removed in vacuo. Flash chromatography, eluting with a gradient of 0-5% MeOH in DCM afforded purified product. Yield: 0.29 g (87%); LC-MS: 290.1 (M+H)+. 1H NMR (400 MHz, CDCl3): δ 8.24 (s, 1H), 4.52 (q, 2H), 3.90 (s, 2H), 3.39 (t, 4H), 2.19 (quin, 2H), 1.45 (t, 3H).

Workup

  1. waitAfter 10 minutes
  2. customexcess reagents and solvent were removed in vacuo
  3. washFlash chromatography, eluting with a gradient of 0-5% MeOH in DCM
  4. customafforded
  5. custompurified product

Sources & evidence

ORD record
ord-cd00c1fb19e243d0ae655f0743897a94
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

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