Dimethylamine → Methyl 2-[(dimethylamino)methyl]-2'-methylbiphenyl-4-carboxylate

HRID 400746Notes

Reaction equation

HRID 400746 reaction equation
C(O[CH2:5][C:6]1[CH:11]=[C:10]([C:12]([O:14][CH3:15])=[O:13])[CH:9]=[CH:8][C:7]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH3:22])(=O)C.C[CH2:24][N:25](C(C)C)[CH:26](C)C.CS(Cl)(=O)=O.CNC>C(Cl)Cl>[CH3:24][N:25]([CH2:5][C:6]1[CH:11]=[C:10]([C:12]([O:14][CH3:15])=[O:13])[CH:9]=[CH:8][C:7]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH3:22])[CH3:26]

Participants

6

Reactant 4

HCID 674DimethylamineHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 67400282Methyl 2-[(acetyloxy)methyl]-2'-methylbiphenyl-4-carboxylate

Product 1

HCID 66678469Methyl 2-[(dimethylamino)methyl]-2'-methylbiphenyl-4-carboxylateYield 86.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl 2-(hydroxymethyl)-2′-methylbiphenyl-4-carboxylate obtained in step 3 (2.12 g; 8.27 mmol) in DCM (63.6 mL) was added at 0° C. DIEA (7.03 mL; 41.36 mmol) and methanesulfonyl chloride (768 μL; 9.93 mmol) at 0° C. and stirred at 25 min. After this time, dimethylamine (12.41 mL; 2 M; 24.81 mmol) was added to the reaction mixture and stirred at RT for 16 hours. Reaction mixture was partitioned between DCM and an aqueous solution of NaOH (5 M). Purification by silica column chromatography (DCM/[DCM/MeOH 2:1] gradient) gave the title compound as a light yellow solid (2.03 g, 86%). 1H NMR (DMSO-d6) δ 8.27 (d, J=1.4 Hz, 1H), 7.95 (dd, J=7.8, 1.9 Hz, 1H), 7.32-7.18 (m, 4H), 7.06 (d, J=7.3 Hz, 1H), 3.94 (s, 3H), 3.24-3.10 (m, 2H), 2.11 (s, 6H), 2.01 (s, 3H). HPLC (Method A) Rt 2.90 min (Purity 100.0%). LC/MS (Method B): 284.1 (M−H)−.

Workup

  1. customReaction mixture
  2. customwas partitioned between DCM
  3. customPurification by silica column chromatography (DCM/[DCM/MeOH 2:1] gradient)

Sources & evidence

ORD record
ord-a13e410aad704692a71375e5e8e4f026
Source dataset
uspto-grants-2014_06
Patent number
US08741923B2

Reaction notes

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