p-Toluenesulfonic acid → tert-Butyl N-[(10R,11E,14S)-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,11,15,17-heptaen-14-yl]carbamate

HRID 1481290Notes

Reaction equation

HRID 1481290 reaction equation
[CH3:1][C@H:2]([CH:30]=[CH2:31])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]1[CH:17]=[CH:16][N:15]=[C:14]([C@@H:18]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:19]C=C)[CH:13]=1)=[O:4].CC1C=CC(S(O)(=O)=O)=CC=1>ClCCl>[CH3:1][C@H:2]1[C:3](=[O:4])[NH:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH:13]=2)[C@@H:18]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:19][CH:31]=[CH:30]1

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 126739818tert-Butyl N-[(1S)-1-(4-{2-[(2R)-2-methylbut-3-enamido]phenyl}pyridin-2-yl)but-3-en-1-yl]carbamate

Product 1

HCID 126739861tert-Butyl N-[(10R,11E,14S)-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,11,15,17-heptaen-14-yl]carbamateYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a round bottom flask was added 45E (1.34 g, 3.18 mmol), pTsOH (0.665 g, 3.50 mmol), and dichloromethane (265 ml). The clear yellow solution was degassed with argon for 30 min. The reaction was then warmed to 40° C. for 1 h. Then a solution of GrubbsII (0.486 g, 0.572 mmol) in DCM (4 mL) was added dropwise to the reaction mixture. After 4.5 h, the reaction was cooled to rt, washed with sat. NaHCO3, brine, dried over MgSO4, filtered, and concentrated to give brown solid. The residue was purified by silica gel chromatography to give the desired product (0.97 g, 78%) as light brownish foam. 1H NMR (500 MHz, METHANOL-d4) δ 8.57-8.52 (m, 1H), 7.51-7.41 (m, 3H), 7.34-7.30 (m, 1H), 7.28 (dd, J=5.2, 1.7 Hz, 1H), 6.92 (s, 1H), 5.71 (ddd, J=15.3, 10.5, 4.7 Hz, 1H), 4.61 (dd, J=11.4, 3.4 Hz, 1H), 4.39 (dd, J=15.1, 9.4 Hz, 1H), 3.14-3.07 (m, 1H), 2.72 (ddd, J=8.6, 7.2, 3.7 Hz, 1H), 2.05-1.95 (m, 1H), 1.44 (s, 9H), 1.04 (d, J=6.9 Hz, 3H). MS (ESI) m/z: 394.1 (M+H)+.

Workup

  1. customThe clear yellow solution was degassed with argon for 30 min
  2. additionThen a solution of GrubbsII (0.486 g, 0.572 mmol) in DCM (4 mL) was added dropwise to the reaction mixture
  3. temperaturethe reaction was cooled to rt
  4. washwashed with sat. NaHCO3, brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give brown solid
  9. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-cb54db337d0842f787e5073ff3cecec5
Source dataset
uspto-grants-2016_08
Patent number
US09409908B2

Reaction notes

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