Proton sponge → tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-(3-methoxybutoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate

HRID 75753Notes

Reaction equation

HRID 75753 reaction equation
[CH2:1]([C@@H:8]1[C@@H:16]([O:17][CH2:18][CH2:19][CH:20]([OH:22])[CH3:21])[C@H:15]([CH3:23])[O:14][C:13](=[O:24])[C@@H:12]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:11][O:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:33]N(C1C2C(N(C)C)=CC=CC=2C=CC=1)C.F[B-](F)(F)F.C[O+](C)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:1]([C@@H:8]1[C@@H:16]([O:17][CH2:18][CH2:19][CH:20]([O:22][CH3:33])[CH3:21])[C@H:15]([CH3:23])[O:14][C:13](=[O:24])[C@@H:12]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:30])([CH3:29])[CH3:31])[CH2:11][O:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 88675Proton spongeHCID 516892Sodium BicarbonateHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 86701247tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-(3-hydroxybutoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate

Product 1

HCID 86701248tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-(3-methoxybutoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamateYield 84.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-(3-hydroxybutoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate (82 mg, 0.18 mmol, 1.00 equiv) in CH2Cl2 (1.8 mL) were added proton sponge (156 mg, 0.726 mmol, 4.00 equiv) and trimethyloxonium tetrafluoroborate (54 mg, 0.36 mmol, 2.0 equiv). The resulting suspension was stirred at room temperature for 1 h, poured into ½ sat'd NaHCO3 solution (20 mL), and extracted with CH2Cl2 (3×20 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated to provide a yellow oil. Purification by automated silica gel column chromatography (1-6% acetone in CH2Cl2) provided tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-(3-methoxybutoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate (71 mg, 84%) as a sticky oil: 1H NMR (400 MHz, CDCl3) δ 7.32-7.23 (m, 2H), 7.23-7.13 (m, 3H), 5.18 (d, J=6.9 Hz, 1H), 5.02-4.86 (m, 1H), 4.60 (q, J=7.2 Hz, 1H), 3.94-3.75 (m, 2H), 3.75-3.62 (m, 1H), 3.62-3.41 (m, 3H), 3.36 (dd, J=10.5, 6.5 Hz, 1H), 3.33-3.22 (m, 4H), 3.21-3.04 (m, 2H), 2.29 (t, J=12.5 Hz, 1H), 2.00-1.81 (m, 1H), 1.81-1.68 (m, 2H), 1.48 (s, 3H), 1.41 (s, 9H), 1.15 (d, J=6.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 172.21, 154.98, 139.93, 139.88, 129.13, 128.42, 126.10, 85.02, 80.03, 75.51, 75.45, 73.41, 73.39, 72.91, 72.58, 69.09, 68.84, 55.94, 55.89, 53.01, 47.27, 47.14, 37.41, 37.35, 35.14, 35.03, 28.27, 19.09, 18.73.

Workup

  1. extractionextracted with CH2Cl2 (3×20 mL)
  2. dry with materialThe combined organic extracts were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto provide a yellow oil
  6. customPurification by automated silica gel column chromatography (1-6% acetone in CH2Cl2)

Sources & evidence

ORD record
ord-a044963bb99e4eb4bbbfc89de16eac62
Source dataset
uspto-grants-2014_09
Patent number
US08835462B2

Reaction notes

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