HCID 68183220, compound → HCID 68183404, compound

HRID 1615539Notes

Reaction equation

HRID 1615539 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9]/[CH:10]=[C:11](/[C:19]1[N:20]=[C:21]([N:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)[S:22][C:23]=1[C:24]([O:26][CH2:27][CH3:28])=[O:25])\[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>C(O)C.[OH-].[Pd+2].[OH-]>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH:11]([C:19]1[N:20]=[C:21]([N:29]2[CH2:30][CH2:31][O:32][CH2:33][CH2:34]2)[S:22][C:23]=1[C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 2

HCID 68183220HCID 68183220, compoundHCID 178418361HCID 178418361, compound2×

Product 1

HCID 68183404HCID 68183404, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalyst3×HCID 702EthanolSolvent

Procedure

To a solution of ethyl 4-[(1E)-3-[(tert-butoxycarbonyl)amino]-1-(4-chlorophenyl)prop-1-en-1-yl]-2-(morpholin-4-yl)-1,3-thiazole-5-carboxylate (0.328 g, 0.646 mmol) in ethanol (8 mL) in a Parr bottle under an atmosphere of argon was added palladium hydroxide (0.0323 g, 0.230 mmol). The flask was purged several times with argon then filled with hydrogen to 60 psi and rapidly stirred at room temperature for 3 hours. The reaction was incomplete by LCMS. An additional portion of palladium hydroxide (0.0300 g, 0.214 mmol) was added and the reaction was stirred at room temperature under 60 psi hydrogen for 16 hours. There was further progress by LCMS but still incomplete reaction, so another portion of palladium hydroxide (0.0300 g, 0.214 mmol) was added and the reaction was stirred at room temperature under 60 psi hydrogen for 3 days. The mixture was filtered through celite, the celite was washed with methanol to extract all product, and the filtrate was concentrated. The residue was purified using column chromatography on silica gel (24 g Analogix column, gradient hexane to 40% EA in hexane over 15 minutes) to give the product (0.286 g, 87%). LCMS: (AA) ES+ 510, 512. 1H NMR (300 MHz, d4-MeOH) δ: 7.40 (d, J=8.5 Hz, 2H), 7.23 (d, J=8.5 Hz, 2H), 5.02 (dd, J=8.9, 6.6 Hz, 1H), 4.24 (q, J=6.8 Hz, 2H), 3.86-3.70 (m, 4H), 3.61-3.45 (m, 4H), 3.02-2.85 (m, 2H), 2.42-2.21 (m, 1H), 2.18-2.01 (m, 1H), 1.40 (s, 9H), 1.30 (t, J=7.1 Hz, 3H).

Workup

  1. customThe flask was purged several times with argon
  2. additionthen filled with hydrogen to 60 psi
  3. customby LCMS but still incomplete reaction
  4. filtrationThe mixture was filtered through celite
  5. washthe celite was washed with methanol
  6. extractionto extract all product
  7. concentrationthe filtrate was concentrated
  8. customThe residue was purified
  9. customon silica gel (24 g Analogix column, gradient hexane to 40% EA in hexane over 15 minutes)

Sources & evidence

ORD record
ord-a6ffe122bc2c4a6387d381e8269edf75
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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