Tetrahydrofuran → Ancymidol

HRID 1754231Notes

Reaction equation

HRID 1754231 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[Li+].[Cl-].COC([C:17]1[C:22]([C:23]([C:25]2[C:26]([CH:31](OC)[C:32]3[CH:37]=[CH:36]C=CC=3)=NC=NC=2)=[O:24])=[CH:21][N:20]=[CH:19][N:18]=1)C1C=CC=CC=1.C1C[O:43][CH2:42]C1>[Cl-].[Cl-].[Zn+2]>[CH3:42][O:43][C:32]1[CH:31]=[CH:26][C:25]([C:23]([OH:24])([C:22]2[CH:17]=[N:18][CH:19]=[N:20][CH:21]=2)[CH:1]2[CH2:3][CH2:2]2)=[CH:36][CH:37]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 433294Lithium ChlorideHCID 68327731HCID 68327731, compoundHCID 178418630HCID 178418630, compound

Product 1

HCID 25572AncymidolYield 31%

Reagents, catalysts & solvents 1

HCID 3007855ZincchlorideCatalyst

Procedure

To a solution of cyclopropylmagnesium bromide (0.5 M in THF, 9 mL, 4.5 mmol) was added ZnCl2 (612 mg, 4.5 mmol) and LiCl (0.189 mg, 4.5 mmol). To this clear yellow solution was added 18 (1.00 g, 4.5 mmol) in THF and the mixture was stirred for 4 h at rt before being washed with sat. NH4Cl. The organic layer was diluted with EtOAc and washed with sat. NaHCO3 before being dried and evaporated to a brown gum, which was dissolved in toluene and poured over a plug of silica gel (20 g). The plug was washed with hexane-EtOAc (100 mL). The eluants were evaporated to a yellow oil that solidified upon trituration with hexanes. The solid was filtered and dried to afford 374 mg (31%) of 15 as a white solid. Mp=108-110° C.; 1H NMR (300 MHz, CDCl3) δ ppm 9.06 (s, 1H), 8.48 (s, 2H), 7.82 (d, 2H), 7.03 (d, 2H), 3.99 (s, 3H), 1.08 (m, 1H), 0.50-0.31 (m, 4H).

Workup

  1. washbefore being washed with sat. NH4Cl
  2. additionThe organic layer was diluted with EtOAc
  3. washwashed with sat. NaHCO3
  4. custombefore being dried
  5. customevaporated to a brown gum, which
  6. dissolutionwas dissolved in toluene
  7. additionpoured over a plug of silica gel (20 g)
  8. washThe plug was washed with hexane-EtOAc (100 mL)
  9. customThe eluants were evaporated to a yellow oil that
  10. filtrationThe solid was filtered
  11. customdried

Sources & evidence

ORD record
ord-facea8cd97e1407e921941689feae847
Source dataset
uspto-grants-2015_10
Patent number
US09169216B2

Reaction notes

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