1-Chloro-N,N-2-trimethylpropenylamine → 3-[3-(benzyloxycarbonylpiperidin-4-yl)acryloyl]-(4R,5S)-1,5-dimethyl-4-phenyl-2-imidazolidinone

HRID 458947Notes

Reaction equation

HRID 458947 reaction equation
ClC(N(C)C)=C(C)C.[CH2:9]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([CH:25]=[CH:26][C:27]([OH:29])=O)[CH2:21][CH2:20]1)=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:40][N:41]1[C@@H:45]([CH3:46])[C@@H:44]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[NH:43][C:42]1=[O:53]>C1COCC1.O>[CH2:9]([O:16][C:17]([N:19]1[CH2:20][CH2:21][CH:22]([CH:25]=[CH:26][C:27]([N:43]2[C@H:44]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[C@H:45]([CH3:46])[N:41]([CH3:40])[C:42]2=[O:53])=[O:29])[CH2:23][CH2:24]1)=[O:18])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

7

Reactant 4

HCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 2733832Lithium HexamethyldisilazideHCID 6931391(4R,5S)-(-)-1,5-Dimethyl-4-phenyl-2-imidazolidinoneHCID 693600903-(1-Cbz-4-piperidyl)acrylic Acid

Product 1

HCID 694622323-[3-(benzyloxycarbonylpiperidin-4-yl)acryloyl]-(4R,5S)-1,5-dimethyl-4-phenyl-2-imidazolidinone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

1-Chloro-N,N,2-trimethyl-1-propenylamine (1.37 g) was added dropwise over 10 minutes to a solution of 3-(benzyloxycarbonylpiperidin-4-yl)propenoic acid (2.5 g) in THF (20 ml) and the mixture was stirred for 1.5 hours. Lithium bis(trimethylsilyl)amide (8.65 ml)was added to a solution of (4R,5S)-1,5dimethyl4-phenyl-2-imidazolidinone (1.64 g) in THF (20 ml) at −10° C. and the mixture was stirred at −10° C. for 10 minutes, allowed to warm to 0° C. and then cooled again to −10° C. The acid chloride solution (prepared above) was added dropwise and the mixture was allowed to warm to room temperature. The reaction mixture was poured into water (100 ml) and extracted with ethyl acetate (3×50 ml). The combined extracts were dried, evaporated to dryness and the residue was chromatographed on a Bond-Elut column eluted with an ethyl acetate/isohexane mixture (1:1) to give the title compound, yield 3.6 g. NMR (DMSOd6): 0.6 (d, 3H) 0.95 (d, 1H) 1.2 (m, 2H) 1.55 (m, 2H) 2.4 (m, 1H) 2.3 (s, 3H) 2.8 (m, 2H) 3.95 (m, 3H) 5 (s, 2H) 5.3 (d, 1H) 6.9 (m, 1H) 7.1 (m, 2H) 7.2–7.4 (m, 8H).

Workup

  1. stirringthe mixture was stirred at −10° C. for 10 minutes
  2. temperaturecooled again to −10° C
  3. temperatureto warm to room temperature
  4. extractionextracted with ethyl acetate (3×50 ml)
  5. customThe combined extracts were dried
  6. customevaporated to dryness
  7. customthe residue was chromatographed on a Bond-Elut column
  8. washeluted with an ethyl acetate/isohexane mixture (1:1)

Sources & evidence

ORD record
ord-164466afd5f14f3aacced60c65f66236
Source dataset
uspto-grants-2007_03
Patent number
US07192973B2

Reaction notes

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