Acetic Acid → (1,3-dimethyl-1H-indol-2-yl)-N-methylmethanamine

HRID 1825947Notes

Reaction equation

HRID 1825947 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([CH3:11])=[C:3]1[CH:12]=O.CN.CO.CC(O)=O.[C:22]([BH3-])#[N:23].[Na+]>>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([CH3:11])=[C:3]1[CH2:12][NH:23][CH3:22]

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 887MethanolHCID 6329MethylamineHCID 27714681,3-dimethyl-1H-indole-2-carbaldehydeHCID 5003444Sodium cyanoborohydride

Product 1

HCID 22139131(1,3-dimethyl-1H-indol-2-yl)-N-methylmethanamineYield 52%

Procedure

To 1,3-dimethyl-1H-indole-2-carboxaldehyde (13.0 g, 75 mmole) was added a solution of 2.0 M methylamine in methanol (150 mL, 300 mmole) and HOAc (4.3 mL, 75 mmole). The solution was stirred at RT for 4 hr, then was cooled to 0° C., and sodium cyanoborohydride (5.0 g, 80 mmole) was added portionwise over 5 min. The reaction was then allowed to warm to RT. After 16 hr, the reaction was concentrated under vacuum and the residue was taken up in Et2O. The solution was washed with 1.0 N NaOH then with brine, dried (Na2SO4), and concentrated to dryness. Flash chromatography on silica gel (95:5 CHCl3/methanol containing 5% NH4OH) gave the title compound (7.34 g, 52%) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 7.53 (d, J=7.8 Hz, 1 H), 7.26 (d, J=7.8 Hz, 1 H), 7.20 (t, 1 H), 7.09 (t, 1 H), 3.88 (s, 2 H), 3.76 (s, 3 H), 2.46 (s, 3 H), 2.32 (s, 3 H), 1.36 (br s, 1 H).

Workup

  1. temperaturewas cooled to 0° C.
  2. temperatureto warm to RT
  3. waitAfter 16 hr
  4. concentrationthe reaction was concentrated under vacuum
  5. washThe solution was washed with 1.0 N NaOH
  6. dry with materialwith brine, dried (Na2SO4)
  7. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-b103e2a6e82d4d5ea10e28b78003eb69
Source dataset
uspto-grants-2006_05
Patent number
US07049310B2

Reaction notes

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