Tetrahydrofuran → tert-butyl (1S,3S)-3-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-4-methyl-1-((S)-oxiran-2-yl)pentylcarbamate

HRID 660390Notes

Reaction equation

HRID 660390 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([CH2:15][C@H:16]([CH:29]([CH3:31])[CH3:30])[CH2:17][C@H:18]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:19]=[O:20])[CH:13]=2)[CH:8]=[N:7]1.[CH2:32]1COCC1>>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([CH2:15][C@H:16]([CH:29]([CH3:31])[CH3:30])[CH2:17][C@H:18]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:26])([CH3:25])[CH3:27])[C@H:19]3[CH2:32][O:20]3)[CH:13]=2)[CH:8]=[N:7]1

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 59630972tert-butyl (2S,4S)-4-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-5-methyl-1-oxohexan-2-ylcarbamate

Product 1

HCID 86649364tert-butyl (1S,3S)-3-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-4-methyl-1-((S)-oxiran-2-yl)pentylcarbamateYield 48%

Procedure

A flame dried 100-mL, round-bottom flask was charged with sodium hydride (1.45 g, 60.0 mmol) and trimethyloxosulfonium iodide (8.0 g, 36 mmol). The flask was evacuated and refilled with N2, and dry DMSO (50 mL) was added. The mixture was stirred at rt for 2 h to give a solution of the sulfur ylid. A second 100-mL, round-bottom flask was charged with tert-butyl (2S,4S)-4-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-5-methyl-1-oxohexan-2-ylcarbamate (830 mg, 1.92 mmol) and THF (10 mL). The flask was evacuated and refilled with N2, and the sulfur ylid solution (6.0 mL) was added through a cannula. The resulting mixture was stirred for 2-3 h at rt. The reaction mixture was quenched with brine and extracted with ethyl acetate (3×25 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by chromatography to afford tert-butyl (1S,3S)-3-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-4-methyl-1-((S)-oxiran-2-yl)pentylcarbamate (410 mg, 48%). 1H NMR (400 MHz, CDCl3): 0.81-0.92 (m, 5H), 1.26 (m, 2H), 1.47 (s, 6H), 1.65 (m, 6H), 2.17 (m, 2H), 2.68 (m, 1H), 2.95 (m, 1H), 3.30 (s, 3H), 4.11 (m, 1H), 4.47 (m, 2H), 6.99 (m, 1H), 7.21 (m, 1H), 7.60 (m, 1H), 7.95 (m, 1H); MS: 446 (M++1)

Workup

  1. customThe flask was evacuated
  2. additionrefilled with N2
  3. additionthe sulfur ylid solution (6.0 mL) was added through a cannula
  4. customThe reaction mixture was quenched with brine
  5. extractionextracted with ethyl acetate (3×25 mL)
  6. dry with materialThe combined organic phases were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-3fe3cfa44340455b87eeb5fb4243c723
Source dataset
uspto-grants-2011_12
Patent number
US08084485B2

Reaction notes

Loading…