Triethylamine → 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(5-methylpyridin-2-yl)cyclopropanecarboxamide

HRID 338569Notes

Reaction equation

HRID 338569 reaction equation
[F:1][C:2]1([F:17])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([OH:16])=O)[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.S(Cl)(Cl)=O.[CH3:22][C:23]1[CH:24]=[CH:25][C:26]([NH2:29])=[N:27][CH:28]=1.C(N(CC)CC)C>ClCCl.CN(C)C=O>[F:17][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:29][C:26]4[CH:25]=[CH:24][C:23]([CH3:22])=[CH:28][N:27]=4)=[O:16])[CH2:12][CH2:13]3)=[CH:10][C:4]=2[O:3]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 153482-Amino-5-methylpyridineHCID 24386Thionyl ChlorideHCID 442061031-(2,2-Difluoro-1,3-benzodioxol-5-yl)cyclopropanecarboxylic acid

Product 1

HCID 442365941-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(5-methylpyridin-2-yl)cyclopropanecarboxamideYield 48.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxylic acid (2.32 g, 9.58 mmol) was placed in an oven-dried flask under nitrogen. Thionyl chloride (3 mL) and N,N-dimethylformamide (0.3 mL) were added and the solution was allowed to stir for 30 minutes at room temperature. The excess thionyl chloride was removed under vacuum and the resulting solid was suspended in anhydrous dichloromethane (10 mL). This solution was then slowly added to a solution 5-methylpyridin-2-amine (0.798 g, 7.38 mmol) in anhydrous dichloromethane (10 mL) containing triethylamine (4.11 mL, 29.5 mmol). The resulting mixture was allowed to stir for 15 hours at room temperature. The crude product was then washed two times with a 1M aqueous solution of hydrochloric acid, two times with a saturated aqueous solution of sodium bicarbonate, and finally two times with a saturated aqueous solution of sodium chloride. The organic layer was dried over sodium sulfate, evaporated to near dryness, and then purified on 120 g of silica gel utilizing a gradient of 0-30% ethyl acetate in hexanes to yield the pure product (1.20 g, 3.60 mmol, 48.7%). ESI-MS m/z calc. 332.1. found 333.1 (M+1)+. Retention time 1.48 minutes.

Workup

  1. customThe excess thionyl chloride was removed under vacuum
  2. stirringto stir for 15 hours at room temperature
  3. washThe crude product was then washed two times with a 1M aqueous solution of hydrochloric acid, two times with a saturated aqueous solution of sodium bicarbonate, and finally two times with a saturated aqueous solution of sodium chloride
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. customevaporated
  6. custompurified on 120 g of silica gel utilizing a gradient of 0-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-c0e87e260f8044ca96efd3220aa00328
Source dataset
uspto-grants-2014_11
Patent number
US08889875B2

Reaction notes

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