3,4-Dichlorobenzyl chloride → HCID 66924343, compound

HRID 2177017Notes

Reaction equation

HRID 2177017 reaction equation
Cl.[F:2][C:3]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[C:4]=1[C:5]#[N:6].[Cl:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][C:27]=1[Cl:28])[CH2:23]Cl.C(N(CC)CC)C>>[Cl:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][C:27]=1[Cl:28])[CH2:23][N:16]1[CH2:17][CH2:18][CH:13]([CH2:12][O:11][C:7]2[CH:8]=[CH:9][CH:10]=[C:3]([F:2])[C:4]=2[C:5]#[N:6])[CH2:14][CH2:15]1

Participants

4

Reactant 3

HCID 76093,4-Dichlorobenzyl chlorideHCID 8471TriethylamineHCID 669243782-Fluoro-6-(piperidin-4-ylmethoxy)-benzonitrile hydrochloride

Product 1

HCID 66924343HCID 66924343, compoundYield 73%

Procedure

A mixture of 2-fluoro-6-(piperidin-4-ylmethoxy)-benzonitrile hydrochloride (240 mg; 0.89 mmol) (Example 126, Step 3) was heated with 3,4-dichlorobenzyl chloride (0.15 mL; 2.0 mmol) and triethylamine (0.3 mL; 2.0 mmol) to 50° C. for 16 hours. Reaction was cooled and quenched with dilute HCl and mixture extracted with ethyl acetate (2×20 mL). Combined organics washed with water, saturated sodium bicarbonate, brine and dried over Na2SO4. Crude material was purified by chromatography using 0.5-2% methanol/DCM gradient to afford 2-[1-(3,4-dichloro-benzyl)-piperidin-4-ylmethoxy]-6-fluoro-benzonitrile as a yellow oil. (280 mg; 73% yield).

Workup

  1. customReaction
  2. temperaturewas cooled
  3. customquenched with dilute HCl and mixture
  4. extractionextracted with ethyl acetate (2×20 mL)
  5. washCombined organics washed with water, saturated sodium bicarbonate, brine
  6. dry with materialdried over Na2SO4
  7. customCrude material was purified by chromatography

Sources & evidence

ORD record
ord-9575f5bd241f4c0abc2c5beb1af07039
Source dataset
uspto-grants-2015_06
Patent number
US09067897B2

Reaction notes

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