Borane → HCID 86614039, compound

HRID 1727218Notes

Reaction equation

HRID 1727218 reaction equation
[Cl:1][C:2]1[C:11]2[N:10]([CH3:12])[O:9][C@H:8]3[NH:13][C@H:14]([C:16]([O:18][C@@H:19]4[C@:28]5([OH:29])[C@H:23]([C@H:24]([C:31]([CH3:33])=[CH2:32])[CH2:25][CH2:26][C@H:27]5[CH3:30])[CH:22]=[C:21]([CH3:34])[C@H:20]4[O:35][C:36](=[O:38])[CH3:37])=[O:17])[CH2:15][C@@:7]3([OH:39])[C:6]=2[CH:5]=[CH:4][CH:3]=1.B.C[N+]1([O-])CC[O:45]CC1>O1CCCC1>[Cl:1][C:2]1[C:11]2[N:10]([CH3:12])[O:9][C@H:8]3[NH:13][C@H:14]([C:16]([O:18][C@@H:19]4[C@:28]5([OH:29])[C@@H:23]([C@H:24]([CH:31]([CH3:33])[CH2:32][OH:45])[CH2:25][CH2:26][C@H:27]5[CH3:30])[CH:22]=[C:21]([CH3:34])[C@H:20]4[O:35][C:36](=[O:38])[CH3:37])=[O:17])[CH2:15][C@@:7]3([OH:39])[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6331Borane2×HCID 82029Methyl morpholine oxideHCID 86614034HCID 86614034, compound

Product 1

HCID 86614039HCID 86614039, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1S,2R,4aS,5R,8R,8aR)-2-(acetyloxy)-8a-hydroxy-3,8-dimethyl-5-(1-methylethenyl)-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl (2S,3aR,9bR)-6-chloro-9b -hydroxy-5-methyl-1,2,3,3a,5,9b-hexahydropyrrolo[2,3-c][2,1]benzoxazine-2-carboxylate (Preparation 1, 500 mg, 0.89 mmol) in tetrahydrofuran (8 ml) at −10° C. under nitrogen was added borane (1M solution in tetrahydrofuran, 2 ml, 2 mmol) and the resulting mixture stirred and allowed to come to room temperature. After 5 hours borane (1M solution in tetrahydrofuran, 1 ml, 1 mmol) was added and the reaction stirred at room temperature for 18 h. To the reaction mixture was added 4-methylmorpholine N-oxide (600 mg, 5.1 mmol) and the mixture heated to gentle reflux for 3 hours. The reaction mixture was concentrated in vacuo and the residue treated with water (30 ml) and extracted with ethyl acetate (2×30 ml). The combined organic extracts were washed with saturated aqueous sodium chloride solution, dried (MgSO4) and the solvent removed in vacuo to give an orange glass. The crude product was purified by column chromatography on silica eluting with hexane:ethyl acetate (2:1 then 1:1) and then ethyl acetate. The pure fractions were combined and concentrated in vacuo to give a the title product as a yellow solid (132 mg, 26%).

Workup

  1. customto come to room temperature
  2. stirringthe reaction stirred at room temperature for 18 h
  3. temperaturethe mixture heated
  4. temperatureto gentle reflux for 3 hours
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. additionthe residue treated with water (30 ml)
  7. extractionextracted with ethyl acetate (2×30 ml)
  8. washThe combined organic extracts were washed with saturated aqueous sodium chloride solution
  9. dry with materialdried (MgSO4)
  10. customthe solvent removed in vacuo
  11. customto give an orange glass
  12. customThe crude product was purified by column chromatography on silica eluting with hexane:ethyl acetate (2:1
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-421a7f33f55b46aeb22f51f4fd374325
Source dataset
uspto-grants-2009_02
Patent number
US07494992B2

Reaction notes

Loading…