Methyl Acrylate → HCID 67074477, compound

HRID 2095510Notes

Reaction equation

HRID 2095510 reaction equation
C(OC(=O)[NH:10][C@H:11]([CH3:25])[CH2:12][N:13]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:15][CH2:16][OH:17])C1C=CC=CC=1.[H][H].[C:29]([O:33][CH3:34])(=[O:32])[CH:30]=[CH2:31].[Cl:35][C:36]1[CH:37]=[C:38]([CH:44]=[CH:45][CH:46]=1)[CH:39]=[CH:40][C:41](Cl)=[O:42].C(N(CC)CC)C>CO.C(Cl)Cl.[Pd]>[CH3:34][O:33][C:29](=[O:32])[CH2:30][CH2:31][N:10]([C@H:11]([CH3:25])[CH2:12][N:13]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:15][CH2:16][OH:17])[C:41](=[O:42])/[CH:40]=[CH:39]/[C:38]1[CH:44]=[CH:45][CH:46]=[C:36]([Cl:35])[CH:37]=1

Participants

9

Reactant 5

HCID 7294Methyl AcrylateHCID 8471TriethylamineHCID 53411290HCID 53411290, compoundHCID 67074022HCID 67074022, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 67074477HCID 67074477, compoundYield 64%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To 45.6 g (0.12 mol) of {(R)-2-[tert-Butoxycarbonyl-(3-hydroxy-propyl)-amino]-1-methyl-ethyl}-carbamic acid benzyl ester in 300 ml of MeOH was added 5 g of 10% Pd/C and the mixture was stirred under 1 atmosphere (balloon) of hydrogen for 2 h. The mixture was then filtered through Hyflo (washing with MeOH) and reconcentrated to around 150 ml volume. 11.2 ml (0.12 mol) of methyl acrylate was added and the mixture stirred for 16 h after which time the reaction was concentrated to dryness, the residue redissolved in 50 ml CH2Cl2, cooled to 0° C. and rapidly added via cannula a to a cooled (−15° C.) solution of 24.3 g (0.12 mol) of 3-chloro-cinnamoyl chloride and 24 ml (0.17 mol) of triethylamine in 200 ml of CH2Cl2. On completion of the addition the reaction was stirred for a further 15 minutes after which time the reaction was washed with 10% citric acid solution, sat. aq. NaHCO3, dried (Na2SO4) and concentrated. Purification on a SiO2-column (n-heptane/EtOAc 7:3 to 9:1), afforded the titled compound in 64% yield as a colorless gum. MS: 483.3 (MH+, Cl).

Workup

  1. filtrationThe mixture was then filtered through Hyflo (washing with MeOH)
  2. concentrationwas concentrated to dryness
  3. dissolutionthe residue redissolved in 50 ml CH2Cl2
  4. additionrapidly added via cannula a to
  5. additionOn completion of the addition the reaction
  6. stirringwas stirred for a further 15 minutes after which time the reaction
  7. washwas washed with 10% citric acid solution, sat. aq. NaHCO3
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customPurification on a SiO2-column (n-heptane/EtOAc 7:3 to 9:1)

Sources & evidence

ORD record
ord-b3e0e93e92f84189adf5de71bf33c750
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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