Triethylamine → HCID 86696517, compound

HRID 1615920Notes

Reaction equation

HRID 1615920 reaction equation
O[CH2:2][CH:3]1[CH2:5][CH:4]1[C:6]1[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=1[C:8]#[N:9].C([N:16](CC)CC)C.CS(Cl)(=O)=O.[OH-].[NH4+]>C(Cl)Cl.C(#N)C>[NH2:16][CH2:2][CH:3]1[CH2:5][CH:4]1[C:6]1[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=1[C:8]#[N:9]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 14923Ammonium HydroxideHCID 31297Methanesulfonyl chlorideHCID 86696516HCID 86696516, compound

Product 1

HCID 86696517HCID 86696517, compoundYield 13%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A cold solution of 2-(2-(hydroxymethyl)cyclopropyl)benzonitrile (425 mg, 2.454 mmol) in methylene chloride (15 mL), and triethyl amine (1.368 mL, 9.81 mmol) was treated with methanesulfonyl chloride (0.287 mL, 3.68 mmol) dropwise with ice bath cooling. The cooling bath was removed, the reaction warmed to rt for 1 hr. The reaction was diluted with methylene chloride washed with water and brine, dried over magnesium sulfate, and concentrated to give a wax. A solution of the material in acetonitrile (15 mL) and ammonium hydroxide (2 mL, 51.4 mmol) was stirred for 16 h at rt. The reaction was concentrated to about ½ volume and diluted with ether. The suspension was extracted with 1N HCl. The acid extracts were made basic with 50% sodium hydroxide, then extracted with methylene chloride (4×). The organics were dried potassium carbonate and concentrated. The resulting dark wax (400 mg) was then purified on silica gel using 1-20% MeOH/methylene chloride to give an orange wax. The wax was triturated with acetone to give 2-(2-(aminomethyl)cyclopropyl)benzonitrile as a white solid (55 mg, 13%). 1H NMR (400 MHz, DMSO-d6) δ 7.91 (br. s., 2H), 7.80 (dd, J=7.8, 1.0 Hz, 1H), 7.65 (td, J=7.8, 1.3 Hz, 1H), 7.40 (td, J=7.6, 1.1 Hz, 1H), 7.20 (d, J=7.8 Hz, 1H), 2.97 (t, J=6.9 Hz, 2H), 2.32-2.19 (m, 1H), 1.68-1.48 (m, 1H), 1.23 (dt, J=8.8, 5.2 Hz, 1H), 1.10 (dt, J=8.7, 5.2 Hz, 1H). LCMS: M+1=173.05.

Workup

  1. temperaturecooling
  2. customThe cooling bath was removed
  3. additionThe reaction was diluted with methylene chloride
  4. washwashed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customto give a wax
  8. concentrationThe reaction was concentrated to about ½ volume
  9. additiondiluted with ether
  10. extractionThe suspension was extracted with 1N HCl
  11. extractionextracted with methylene chloride (4×)
  12. concentrationconcentrated
  13. customThe resulting dark wax (400 mg) was then purified on silica gel using 1-20% MeOH/methylene chloride
  14. customto give an orange wax
  15. customThe wax was triturated with acetone

Sources & evidence

ORD record
ord-8d030ef5f6824701b00e983c6132019f
Source dataset
uspto-grants-2014_07
Patent number
US08765767B2

Reaction notes

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