Triethylamine → (3-Chloro-8-dimethylaminomethyl-naphthalen-2-yl)-acetonitrile

HRID 505241Notes

Reaction equation

HRID 505241 reaction equation
[CH2:1]([N:3](CC)CC)C.[Cl:8][C:9]1[C:10]([CH2:23]O)=[CH:11][C:12]2[C:17]([CH:18]=1)=[CH:16][CH:15]=[CH:14][C:13]=2[CH2:19][N:20]([CH3:22])[CH3:21].CS(Cl)(=O)=O.[C-]#N.[K+]>C(Cl)Cl.O>[Cl:8][C:9]1[C:10]([CH2:23][C:1]#[N:3])=[CH:11][C:12]2[C:17]([CH:18]=1)=[CH:16][CH:15]=[CH:14][C:13]=2[CH2:19][N:20]([CH3:22])[CH3:21]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9032Potassium CyanideHCID 31297Methanesulfonyl chlorideHCID 66882407{3-Chloro-8-[(dimethylamino)methyl]naphthalen-2-yl}methanol

Product 1

HCID 66882331(3-Chloro-8-dimethylaminomethyl-naphthalen-2-yl)-acetonitrileYield 48%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

Triethylamine (0.12 ml, 0.87 mmol, 2.0 equiv) was added to a solution of (3-chloro-8-dimethylaminomethyl-naphthalen-2-yl)-methanol (109 mg, 0.44 mmol) in CH2Cl2 (1.5 ml). At −25° C., a solution of methanesulfonyl chloride (0.05 ml, 0.66 mmol, 1.5 equiv) in CH2Cl2 (1.5 ml) was then added dropwise. After 15 minutes at 0° C., cold water (4° C., 10 ml) was added, and the mixture was extracted with CH2Cl2 (2×40 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude mesylate was dissolved in N,N-dimethylformamide (2 ml) and treated at 0° C. with potassium cyanide (39 mg, 0.60 mmol, 1.0 equiv). The reaction mixture was stirred at room temperature for 2 hours, until TLC analysis indicated complete conversion. After dilution with water (50 ml), the mixture was extracted with CH2Cl2 (2×200 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. Purification via flash chromatography (hexane/EtOAc 100:0 to 80:20) afforded the title compound (54 mg, 48%, mixture of 2 regioisomers). The regioisomers could be separated by preparative HPLC. Data for (3-chloro-8-dimethylaminomethyl-naphthalen-2-yl)-acetonitrile: 1H NMR (400 MHz, CDCl3): δ=8.20 (s, 1H), 8.04 (s, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.72 (d, J=6.6 Hz, 1H), 7.55 (dd, J=8.4/6.6 Hz, 1H), 4.59 (s, 2H), 3.96 (s, 2H), 2.78 (s, 6H). MS (ES+): 259 (M+H)+.

Workup

  1. extractionthe mixture was extracted with CH2Cl2 (2×40 ml)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe crude mesylate was dissolved in N,N-dimethylformamide (2 ml)
  6. extractionAfter dilution with water (50 ml), the mixture was extracted with CH2Cl2 (2×200 ml)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification via flash chromatography (hexane/EtOAc 100:0 to 80:20)

Sources & evidence

ORD record
ord-5e089cbb3dbd48cc81592cdb3cb48580
Source dataset
uspto-grants-2010_08
Patent number
US07781438B2

Reaction notes

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