Water → N,N-Diethyl-2-(hydroxymethyl)benzamide

HRID 1690712Notes

Reaction equation

HRID 1690712 reaction equation
[Cl-].[Cl-].[Cl-].[Al+3].[CH2:5]([NH:7][CH2:8][CH3:9])[CH3:6].[C:10]1([C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:13][O:12]1)=[O:11].O>ClC(Cl)C>[CH2:5]([N:7]([CH2:8][CH3:9])[C:10](=[O:11])[C:19]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH2:13][OH:12])[CH3:6]

Participants

6

Reactant 4

HCID 962WaterHCID 6885PhthalideHCID 8021DiethylamineHCID 6451240Aluminum(III) Chloride

Product 1

HCID 13660025N,N-Diethyl-2-(hydroxymethyl)benzamide

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent2×

Procedure

To a suspension of aluminium trichloride (12.67 g, 94.98 mmol) in dichloroethane (40 mL) is added diethylamine (13.5 g, 182.7 mmol) in dichloroethane (20 mL) while the temperature is maintained below 25° C. with an ice-bath. After another 25 min at r.t., phthalide (10.00 g, 74.5 mmol) is added in three portions and formation of a precipitate is observed. After 45 min, water and ice are added and the mixture is stirred for 30 min and filtered through celite. The aqueous phase is extracted with dichloromethane. After drying the combined organic phase over MgSO4 and filtering through a cotton plug, the volatiles are removed in vacuo to give an orange residue, which is purified by silica gel flash chromatography (dichloromethane-methanol, 49:1 to 97:3 to 19:1) to give N,N-diethyl-2-hydroxymethyl-benzamide as an orange oil; 1H NMR (400 MHz) δ 1.09 (3 H, t, J=7.0 Hz), 1.28 (3 H, t, J=7.0 Hz), 3.24 (2 H, q, J=7.0 Hz), 3.55 (1 H, t, J=6.8 Hz), 3.58 (2 H, q, J=7.0 Hz), 4.52 (2 H, d, J=6.8 Hz), 7.24 (1 H, dd, J=7.4, 1.5 Hz), 7.32 (1 H, td, J=7.4, 1.5 Hz), 7.39 (1 H, td, J=7.4, 1.5 Hz), 7.44 (1 H, td, J=7.4, 1.5 Hz).

Workup

  1. temperatureis maintained below 25° C. with an ice-bath
  2. waitAfter 45 min
  3. filtrationfiltered through celite
  4. extractionThe aqueous phase is extracted with dichloromethane
  5. dry with materialAfter drying the combined organic phase over MgSO4
  6. filtrationfiltering through a cotton plug
  7. customthe volatiles are removed in vacuo
  8. customto give an orange residue, which
  9. customis purified by silica gel flash chromatography (dichloromethane-methanol, 49:1 to 97:3 to 19:1)

Sources & evidence

ORD record
ord-9f89af6df88c43088102633abd4b1854
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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