Proton sponge → HCID 117982169, compound

HRID 1776109Notes

Reaction equation

HRID 1776109 reaction equation
[C:1]([O:5][C:6](=[O:29])[NH:7][C@H:8]1[CH2:16][CH2:15][CH2:14][C@H:13]([CH2:17][CH2:18][OH:19])[C@@H:12]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C@H:11]([CH3:27])[O:10][C:9]1=[O:28])([CH3:4])([CH3:3])[CH3:2].[CH3:30]N(C1C2C(N(C)C)=CC=CC=2C=CC=1)C.F[B-](F)(F)F.C[O+](C)C>C(Cl)Cl>[C:1]([O:5][C:6](=[O:29])[NH:7][C@H:8]1[CH2:16][CH2:15][CH2:14][C@H:13]([CH2:17][CH2:18][O:19][CH3:30])[C@@H:12]([O:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C@H:11]([CH3:27])[O:10][C:9]1=[O:28])([CH3:2])([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 88675Proton spongeHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 117982168HCID 117982168, compound

Product 1

HCID 117982169HCID 117982169, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl((3S,7R,8R,9S)-7-(2-hydroxyethyl)-9-methyl-2-oxo-8-phenoxyoxonan-3-yl)carbamate (400 mg, 0.982 mmol) and Proton Sponge® (841 mg, 3.93 mmol) in anhydrous CH2Cl2 (10 mL) at 0° C. (icewater bath) was added trimethyloxonium tetrafluoroborate (290 mg, 1.963 mmol; weighed under N2), and the resulting mixture was stirred at 0° C. for 3 h, quenched with 1N HCl (20 mL), and extracted with CH2Cl2 (3×20 mL). The organic extracts were combined, dried over Na2SO4, filtered, and concentrated to provide an oily white solid, which was purified by column chromatography on SiO2 (5→20% acetone/hexanes) to provide the title compound as a white, crystalline solid (321 mg, 78%): 1H NMR (400 MHz, CDCl3) δ 7.27 (t, J=8.0 Hz, 2H), 6.94 (dd, J=7.7, 3.3 Hz, 3H), 5.10 (d, J=8.1 Hz, 1H), 5.08-4.98 (m, 1H), 4.20 (q, J=7.9, 6.9 Hz, 2H), 3.36 (t, J=6.5 Hz, 2H), 3.25 (s, 3H), 2.27 (dt, J=13.3, 6.8 Hz, 1H), 1.88 (ddt, J=10.8, 6.9, 3.9 Hz, 2H), 1.83-1.71 (m, 1H), 1.70-1.61 (m, 1H), 1.60-1.52 (m, 1H), 1.44 (s, 10H), 1.28 (d, J=6.5 Hz, 3H), 1.25-1.16 (m, 1H), 1.16-1.05 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 173.28, 159.46, 154.90, 129.61, 121.05, 115.38, 81.12, 79.86, 74.71, 70.79, 58.42, 52.99, 40.09, 34.12, 30.53, 28.33, 28.15, 19.07, 18.36; ESIMS m/z 422.3 ([M+H]+), 444.3 ([M+Na]+).

Workup

  1. customquenched with 1N HCl (20 mL)
  2. extractionextracted with CH2Cl2 (3×20 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto provide an oily white solid, which
  7. customwas purified by column chromatography on SiO2 (5→20% acetone/hexanes)

Sources & evidence

ORD record
ord-d0c9dde8b47143d7905a66b346f4ab66
Source dataset
uspto-grants-2016_02
Patent number
US09265253B2

Reaction notes

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