Benzoyl chloride → HCID 68494598, compound

HRID 1944214Notes

Reaction equation

HRID 1944214 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[CH:15]([CH3:21])[NH:14][C:13]([CH3:23])([CH3:22])[CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:31][O:32][C:33]1[CH:34]=[C:35]([CH:39]=[C:40]([O:44][CH3:45])[C:41]=1[O:42][CH3:43])[C:36](Cl)=[O:37].C(Cl)(=O)C1C=CC=CC=1>C(Cl)Cl.O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[CH:15]([CH3:21])[N:14]([C:36]([C:35]1[CH:39]=[C:40]([O:44][CH3:45])[C:41]([O:42][CH3:43])=[C:33]([O:32][CH3:31])[CH:34]=1)=[O:37])[C:13]([CH3:22])([CH3:23])[CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 78282Benzoyl chloride, 3,4,5-trimethoxy-HCID 68498071HCID 68498071, compound

Product 1

HCID 68494598HCID 68494598, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 244 (467 mg, 1.5 mmol) in DCM (10 ml) was added triethyl amine (0.42 ml) and 3,4,5-trimethoxybenzoyl chloride (520 mg, 2.3 mmol). The reaction mixture was stirred at rt for 21 h. TLC analysis indicated the presence of starting material so the reaction mixture was heated in the microwave for 5 min at 60° C. and for 15 min at 80° C. A further 0.5 eq of benzoyl chloride was added and the reaction mixture was heated in the microwave at 80° C. for 15 min. Water (20 ml) was added, the layers separated and the aqueous layer extracted with DCM (3×60 ml). The combined organic phases were washed with sat. aq. sodium hydrogen C(Ar)bonate (60 ml) and brine (60 ml), dried (MgSO4) and concentrated in vacuo. Purification (flashmaster: 20 g, EtOAc/hex then Hex/DCM) afforded the title compound (440 mg, 58%) as a colourless foam. mp 175-177° C. 1H NMR (270 MHz; CDCl3) 1.32 (3H, d, J=6.9 Hz, CH3CH), 1.39 (3H, s, CH3), 1.87 (3H, s, CH3), 2.53 (1H, d, J=15.3 Hz, one of CH2), 3.27 (1H, d, J=15.3 Hz, one of CH2), 3.82 (6H, s, 2×OCH3), 3.86 (3H, s, OCH3), 3.88 (3H, s, OCH3), 4.69 (1H, q, J=6.9 Hz, CHCH3), 5.04 (2H, ABq, J=12.1 Hz, CH2Ph), 6.47 (3H, s, 3×CH), 6.75 (1H, s, CH), 7.25-7.41 (5H, m, 5×CH, phenyl). 13C NMR (100 MHz; CDCl3) 23.43 (CH3), 25.28 (CH3), 29.40 (CH3), 44.18 (CH2), 56.18 (4×OCH3), 57.68 (C), 60.92 (CH), 71.38 (CH2), 102.51 (CH), 111.45 (CH), 112.36 (CH), 127.09 (C), 127.28 (CH), 127.87 (CH), 128.49 (CH), 130.61 (C), 135.07 (C), 136.09 (C), 137.89 (C), 146.88 (C), 149.06 (C), 153.41 (C), 170.97 (C). LC/MS (ES+) tr=1.03 min, m/z 528.27 (M++Na). HPLC tr=2.38 min (>99%). Anal. Calcd. for C30H35NO6: C 71.27, H 6.98, N 2.77. Found: C 71.1, H 6.99, N 2.70%.

Workup

  1. temperaturewas heated in the microwave for 5 min at 60° C. and for 15 min at 80° C
  2. temperaturethe reaction mixture was heated in the microwave at 80° C. for 15 min
  3. customthe layers separated
  4. extractionthe aqueous layer extracted with DCM (3×60 ml)
  5. washThe combined organic phases were washed with sat. aq. sodium hydrogen C(Ar)bonate (60 ml) and brine (60 ml)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customPurification (flashmaster

Sources & evidence

ORD record
ord-be8bbe17940645cfb2bee90e87e53d10
Source dataset
uspto-grants-2013_03
Patent number
US08394825B2

Reaction notes

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