Ethanol → HCID 67192329, compound

HRID 1254237Notes

Reaction equation

HRID 1254237 reaction equation
O[C@@:2]([C@@H:15]1[CH2:20][CH2:19][CH2:18][N:17]([C:21]([NH:23][C@@H:24]([CH2:37][CH:38]2[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]2)[CH2:25][N:26]([CH3:36])[C:27](=[O:35])[O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])=[O:22])[CH2:16]1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:3][CH2:4][CH2:5][CH2:6][O:7][CH3:8].C(O)C>[Ni].O>[CH3:8][O:7][CH2:6][CH2:5][CH2:4][CH2:3][C@H:2]([C@@H:15]1[CH2:20][CH2:19][CH2:18][N:17]([C:21]([NH:23][C@@H:24]([CH2:37][CH:38]2[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43]2)[CH2:25][N:26]([CH3:36])[C:27](=[O:35])[O:28][CH2:29][CH2:30][Si:31]([CH3:32])([CH3:33])[CH3:34])=[O:22])[CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 2

HCID 702EthanolHCID 67190377HCID 67190377, compound

Product 1

HCID 67192329HCID 67192329, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 935NickelCatalyst2×HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A 100-mL round bottom flask was charged with of 2-(trimethylsilyl)ethyl (S)-2-((R)-3-((S)-1-hydroxy-5-methoxy-1-phenylpentyl)piperidine-1-carboxamido)-3-cyclohexylpropyl-methylcarbamate (0.9806 g, 1.59 mol, 1.0 equiv), absolute ethanol (6 mL), and Raney nickel (2.15 g, ca. 20 equiv) (Aldrich Raney® 2800 nickel, slurry in water, washed with distilled water prior to use until the washings were neutral, then washed three times with absolute ethanol and stored under ethanol until needed.) The reaction mixture was heated to 100° C. for 3 h and then stirred at rt overnight. LC-MS showed about 60% conversion. The ethanolic solution was decanted from the catalyst. The catalyst was washed with absolute ethanol three times, the solvent being removed by decanting in each case. The organic solutions were combined and concentrated in vacuo. The residue was purified by reversed-phase HPLC (Phenomenex® Luna 5μ C18(2) 100 A, 250×21.20 mm, 5 micron, 70%→90% CH3CN/H2O, 0.1% CF3COOH over 8 min and then 90% CH3CN/H2O, 0.1% CF3COOH over 16 min, flow rate 25 mL/min) to give of 2-(trimethylsilyl)ethyl (S)-2-((S)-3-((R)-5-methoxy-1-phenylpentyl)-piperidine-1-carboxamido)-3-cyclohexylpropylmethylcarbamate (0.5422 g, 57%). LC-MS (3 min) tR=2.61 min, m/z 624 (M+Na+), 602 (M+H+). 1H NMR (400 MHz, CDCl3) δ 8.28 (br s, 2H), 7.29-7.25 (m, 2H), 7.21-7.17 (m, 1H), 7.09-7.06 (m, 2H), 5.46 (m, 1H), 4.21-4.06 (m, 4H), 3.68-3.59 (m, 2H), 3.33-3.27 (m, 2H), 3.28 (s, 3H), 2.92 (s, 3H), 2.68-2.63 (m, 1H), 2.43-2.29 (m, 2H), 1.80-0.83 (m, 25H), 0.02 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 158.5, 158.0, 142.8, 128.4, 128.2, 126.2, 72.7, 64.3, 58.3, 52.8, 49.4, 49.1, 47.9, 45.1, 41.2, 41.1, 34.7, 34.3, 33.4, 33.3, 32.4, 29.2, 28.7, 26.4, 26.2, 26.1, 25.1, 24.1, 17.7, −1.5.

Workup

  1. washwashed with distilled water
  2. washwashed three times with absolute ethanol
  3. customThe ethanolic solution was decanted from the catalyst
  4. washThe catalyst was washed with absolute ethanol three times
  5. customthe solvent being removed
  6. customby decanting in each case
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by reversed-phase HPLC (Phenomenex® Luna 5μ C18(2) 100 A, 250×21.20 mm, 5 micron, 70%
  9. customover 8 min
  10. wait90% CH3CN/H2O, 0.1% CF3COOH over 16 min

Sources & evidence

ORD record
ord-0e893bd83fa64217a7811d097b06c9cf
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

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