tert-Butanol → Dimethyl 4-(2,6-dichlorophenyl)-2-(2-methoxy-2-oxoethyl)-6-[2-[2-[[2-(tritylamino)ethoxy]methyl]phenyl]ethyl]-1,4-dihydro-3,5-pyridinedicarboxylate

HRID 481000Notes

Reaction equation

HRID 481000 reaction equation
CC(O)(C)C.C[Mg+].[Br-].[NH2:9][C:10]([CH2:16][C:17]([O:19][CH3:20])=[O:18])=[CH:11][C:12]([O:14][CH3:15])=[O:13].[Cl:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:23]=1[CH:29]=[C:30]([C:35](=O)[CH2:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[CH2:44][O:45][CH2:46][CH2:47][NH:48][C:49]([C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1)([C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[C:31]([O:33][CH3:34])=[O:32]>C1COCC1.O.C(O)(=O)C>[Cl:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:23]=1[CH:29]1[C:30]([C:31]([O:33][CH3:34])=[O:32])=[C:35]([CH2:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[CH2:44][O:45][CH2:46][CH2:47][NH:48][C:49]([C:62]2[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=2)([C:56]2[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=2)[C:50]2[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=2)[NH:9][C:10]([CH2:16][C:17]([O:19][CH3:20])=[O:18])=[C:11]1[C:12]([O:14][CH3:15])=[O:13]

Participants

8

Reactant 4

HCID 6386tert-ButanolHCID 253819Dimethyl 3-aminoglutaconateHCID 69684722Methyl 3-(2,6-dichlorophenyl)-2-[3-[2-[[2-(tritylamino)ethoxy]methyl]phenyl]propanoyl]-2-propenoateHCID 178418689HCID 178418689, compound

Product 1

HCID 18765882Dimethyl 4-(2,6-dichlorophenyl)-2-(2-methoxy-2-oxoethyl)-6-[2-[2-[[2-(tritylamino)ethoxy]methyl]phenyl]ethyl]-1,4-dihydro-3,5-pyridinedicarboxylate

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×

Procedure

To a stirred solution of 2-methyl-2-propanol (1.25 g, 16.9 mmol) in anhydrous THF (50 ml) was added dropwise a 0.95 M solution of MeMgBr in THF (17.8 ml, 16.0 mmol) at room temperature under nitrogen atmosphere. The resulting solution was stirred at room temperature for 0.5 hour. Then to the mixture was added a solution of dimethyl 3-amino-2-pentenedioate (1.33 g, 7.66 mmol) in anhydrous THF (20 ml) dropwise at room temperature. The resulting pale yellow solution was stirred at the same temperature for 0.5 hour, then a solution of methyl 3-(2,6-dichlorophenyl)-2-[3-[2-[[2-(tritylamino)ethoxy]methyl]phenyl]propanoyl]-2-propenoate (6.38 mmol) in anhydrous THF (20 ml) was added at room temperature. The reaction mixture was stirred at room temperature for 8 h under nitrogen atmosphere, then acetic acid (3 ml) was added. The resulting mixture was stirred at room temperature for 16 hours. The mixture was poured into water, and the whole was extracted with ethyl acetate (20 ml×2). The combined organic layers were washed with 2N-HClaq. (50 ml) and sat.NaHCO3aq. (50 ml), dried over MgSO4 and concentrated to afford a crude mixture. Purification on silica gel column chromatography eluted with hexane/EtOAc (3/1) to afford the titled compound as a yellow amorphous. (3.80 g, 85%).

Workup

  1. stirringThe resulting pale yellow solution was stirred at the same temperature for 0.5 hour
  2. stirringThe reaction mixture was stirred at room temperature for 8 h under nitrogen atmosphere
  3. stirringThe resulting mixture was stirred at room temperature for 16 hours
  4. extractionthe whole was extracted with ethyl acetate (20 ml×2)
  5. washThe combined organic layers were washed with 2N-HClaq
  6. dry with material(50 ml), dried over MgSO4
  7. concentrationconcentrated
  8. customto afford a crude mixture
  9. customPurification on silica gel column chromatography
  10. washeluted with hexane/EtOAc (3/1)

Sources & evidence

ORD record
ord-22916626b5f14066bb012e1b692987d2
Source dataset
uspto-grants-2003_11
Patent number
US06653313B2

Reaction notes

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