Acetic Acid → 6-{4-[2-(Benzyl-methyl-amino)-ethyl]-phenoxy}-nicotinamide

HRID 130717Notes

Reaction equation

HRID 130717 reaction equation
[CH2:1]([NH:8][CH2:9][CH2:10][C:11]1[CH:26]=[CH:25][C:14]([O:15][C:16]2[CH:24]=[CH:23][C:19]([C:20]([NH2:22])=[O:21])=[CH:18][N:17]=2)=[CH:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:27]C(O)=O.C=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[CH2:1]([N:8]([CH3:27])[CH2:9][CH2:10][C:11]1[CH:26]=[CH:25][C:14]([O:15][C:16]2[CH:24]=[CH:23][C:19]([C:20]([NH2:22])=[O:21])=[CH:18][N:17]=2)=[CH:13][CH:12]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 444340576-(4-(2-(Benzylamino)ethyl)phenoxy)nicotinamide

Product 1

HCID 597302926-{4-[2-(Benzyl-methyl-amino)-ethyl]-phenoxy}-nicotinamide

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

Combine amine (65 mg, 0.20 mmol) from example 1, AcOH (70 μL, 1.2 mmol), formaldehyde (0.6 mmol) and NaBH(OAc)3 (0.40 mmol) in 1,2-DCE (2 mL). Stir the mixture at room temperature overnight. Dilute the mixture with CH2Cl2 and wash with NaHCO3 sat. Extract the aqueous layer with CH2Cl2, combine the organic layers and dry over Na2SO4. Purify by flash chromatography on silica gel (eluent: EtOAc). Electrospray MS M+1 ion=362, 1H-NMR (CDCl3, 400 MHz): 8.58 (d, 1H, J=2.6 Hz), 8.15 (dd, 1H, J=2.6 and 8.6 Hz), 7.32-7.22 (m, 7H), 7.06-7.04 (m, 2H), 6.95 (d, 1H, J=8.6 Hz), 3.61 (bs, 2H), 2.91-2.84 (m, 2H), 2.74-2.66 (m, 2H), 2.32 (s, 3H).

Workup

  1. washwash with NaHCO3 sat.
  2. extractionExtract the aqueous layer with CH2Cl2
  3. dry with materialdry over Na2SO4
  4. customPurify by flash chromatography on silica gel (eluent: EtOAc)

Sources & evidence

ORD record
ord-4768bc6e95d24b8ba69f19154cbd4d6b
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

Loading…