Diethyl Ether → (3R,5S)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-ol

HRID 520792Notes

Reaction equation

HRID 520792 reaction equation
[CH3:1][C:2]([CH3:33])=[CH:3][CH2:4][C@H:5]1[O:7][C@@:6]1([C@@H:9]1[C@:14]2([O:16][CH2:15]2)[CH2:13][CH2:12][C@@H:11]([O:17]C(/C=C/C=C/C=C/C=C/C(O)=O)=O)[C@H:10]1[O:31][CH3:32])[CH3:8].C1CCC(NC2CCCCC2)CC1.[OH-].[Na+].CCOCC.CC(C)=CC[C@H]1O[C@@]1([C@@H]1[C@]2(OC2)CC[C@@H](OC(/C=C/C=C/C=C/C=C/C(O)=O)=O)[C@H]1OC)C>O>[CH3:32][O:31][C@@H:10]1[CH:11]([OH:17])[CH2:12][CH2:13][C@@:14]2([O:16][CH2:15]2)[CH:9]1[C@:6]1([CH3:8])[C@@H:5]([CH2:4][CH:3]=[C:2]([CH3:33])[CH3:1])[O:7]1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 14798Sodium HydroxideHCID 6917655FumagillinHCID 76958970Bicyclohexylammonium fumagillin

Product 1

HCID 88923313(3R,5S)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-ol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

The mixture of fumagillin DCHA salt (10 g, 0.022 mol), 800 mL of 0.1 N NaOH solution in H2O, and 800 mL of Et2O was stirred at RT for 3 h. LC/Mass showed that the fumagillin had been consumed. The mixture was treated with 400 mL of Ether and the layers were separated. The water layer was extracted with ether (3×500 mL) and the combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified on a Biotage (EtOAc/hexanes) to provide ANT-2970 (4.1 g, 6.16 g theoretical, 66%). 1H NMR (300 MHz, CDCl3,) δ 1.21 (s, 3H), 1.65 (s, 3H), 1.75 (s, 3H), 1.90-2.05 (m, 3H), 2.18-2.26 (m, 2H), 2.34-2.39 (m, 2H), 2.55 (d, 1H), 2.59 (t, 1H), 2.92 (m, 1H), 3.48 (s, 3H), 3.62 (dt, 1H), 4.38 (m, 1H), 5.21 (m, 1H); LC-MS 283 (M+1).

Workup

  1. customhad been consumed
  2. additionThe mixture was treated with 400 mL of Ether
  3. customthe layers were separated
  4. extractionThe water layer was extracted with ether (3×500 mL)
  5. dry with materialthe combined organic layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified on a Biotage (EtOAc/hexanes)
  8. customto provide ANT-2970 (4.1 g, 6.16 g theoretical, 66%)

Sources & evidence

ORD record
ord-478fdc09af5b4f909955bcabd0f7fd9e
Source dataset
uspto-grants-2016_05
Patent number
US09328082B2

Reaction notes

Loading…