Diisopropylamine → HCID 57494707, compound

HRID 1986573Notes

Reaction equation

HRID 1986573 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)[C:21]2[CH:33]=[CH:32][CH:31]=[CH:30][C:22]=2[C:23](N(CC)CC)=O)=[C:16]([CH3:43])[CH:15]=1.C1C[O:47]CC1>>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]2[N:20]([CH2:34][C:35]3[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=3)[C:21]3[CH:33]=[CH:32][CH:31]=[CH:30][C:22]=3[CH2:23][C:43](=[O:47])[C:16]=2[CH:15]=1

Participants

5

Reactant 4

HCID 7912DiisopropylamineHCID 8028Tetrahydrofuran2×HCID 57494709HCID 57494709, compoundHCID 178418339Butyllithium

Product 1

HCID 57494707HCID 57494707, compoundYield 59%

Conditions

Temperature
-20 °C

Procedure

To a mixture of diisopropylamine (1.09 mL, 7.8 mmol) and N,N,N,N-tetramethylenediamine (1.17 mL, 7.8 mmol) in dry THF (19 mL) at −20° C. was added n-BuLi (5.54 mL, 1.4 M in hexane) and the resulting mixture was stirred at −20° C. for 5 minutes. Then a mixture of 2[(4-chloro-2-methylphenyl)-(4-methoxybenzyl)-amino]-N,N-diethylbenzamide (189JO26) (1.36 g, 3.1 mmol) in dry THF (38 mL) was added and the resulting mixture was stirred at −20° for 4 h. The reaction was quenched by addition of saturated aqueous NH4Cl-solution. The mixture was diluted with EtOAc, washed with water, dried (Na2SO4), concentrated, and flash chromatographed (SiO2, toluene:heptane, 7:1-1:0) to give 665 mg (59%) of the title compound (189JO27). 1H NMR (CDCl3) d 8.15 (dd, 1H, J=1.8, 8.0 Hz), 7.43 (m, 1H), 7.24 (m, 4H), 7.17 (d, 1H, J=8.6 Hz), 7.12 (dd, 1H, J=2.4, 8.6 Hz), 7.00 (dt, 1H, J=0.8, 7.0 Hz), 6.81 (m, 2H), 5.09 (s, 2H), 4.00 (s, 2H), 3.75 (s, 3H); 13C NMR (CDCl3) d 190.3, 159.1, 149.5, 146.2, 134.1, 132.4, 131.3, 131.1, 129.1, 129.0, 128.6, 127.3, 126.4, 123.4, 121.0, 118.5, 114.2, 55.5, 19.3. MS (ESI) 364 (MH+).

Workup

  1. additionwas added
  2. stirringthe resulting mixture was stirred at −20° for 4 h
  3. customThe reaction was quenched by addition of saturated aqueous NH4Cl-solution
  4. additionThe mixture was diluted with EtOAc
  5. washwashed with water
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customflash chromatographed (SiO2, toluene:heptane, 7:1-1:0)

Sources & evidence

ORD record
ord-89794961bd804019abd76cc69b7a7b3e
Source dataset
uspto-grants-2009_06
Patent number
US07550454B2

Reaction notes

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