Hydrochloric Acid → HCID 71536498, compound

HRID 1473274Notes

Reaction equation

HRID 1473274 reaction equation
[F:1][C:2]1[CH:36]=[CH:35][C:5]([CH2:6][N:7]2[C:11]3[C:12](=[O:30])[N:13]([CH3:29])[C:14]([CH:23]([OH:28])[C:24]([O:26]C)=[O:25])=[C:15]([C:16]4[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=4)[C:10]=3[C:9]3[CH2:31][O:32][CH2:33][CH2:34][C:8]2=3)=[CH:4][CH:3]=1.C(O[C:41]([CH3:44])([CH3:43])[CH3:42])(=O)C.Cl(O)(=O)(=O)=O.[Li+].[OH-].Cl>CO>[C:41]([O:28][CH:23]([C:14]1[N:13]([CH3:29])[C:12](=[O:30])[C:11]2[N:7]([CH2:6][C:5]3[CH:35]=[CH:36][C:2]([F:1])=[CH:3][CH:4]=3)[C:8]3[CH2:34][CH2:33][O:32][CH2:31][C:9]=3[C:10]=2[C:15]=1[C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)[C:24]([OH:26])=[O:25])([CH3:44])([CH3:43])[CH3:42]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 10908tert-Butyl acetateHCID 24247Perchloric AcidHCID 89462837HCID 89462837, compound

Product 1

HCID 71536498HCID 71536498, compoundYield 53.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of methyl 2-(5-(4-fluorobenzyl)-7-methyl-6-oxo-9-(p-tolyl)-1,3,4,5,6,7-hexahydropyrano[3′,4′:4,5]pyrrolo[2,3-c]pyridin-8-yl)-2-hydroxyacetate (26 mg, 0.053 mmol) was dissolved in tert butyl acetate (618 μl, 5.30 mmol), cooled to 0° C. and treated with perchloric acid (7.21 μl, 0.053 mmol) and the reaction vessel was transferred to the fridge. After 72 h (weekend), the reaction mixture was partitioned between EtOAc and sat. aq. NaHCO3 and the organic layer was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was dissolved in THF (0.2 mL) and MeOH (0.2 mL), treated with 2M LiOH (133 μl, 0.265 mmol) and heated to 50° C. After 2 h, The reaction mixture was poured into 1M HCl and extracted with EtOAc. The organic layer was washed with brine, dried (MgSO4), filtered and concentrated. The residue was purified by reverse phase HPLC to afford 2-(tert-butoxy)-2-(5-(4-fluorobenzyl)-7-methyl-6-oxo-9-(p-tolyl)-1,3,4,5,6,7-hexahydropyrano[3′,4′:4,5]pyrrolo[2,3-c]pyridin-8-yl)acetic acid (15 mg, 0.028 mmol, 53.1% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d)=7.50-7.43 (m, 1H), 7.17 (none, 5H), 7.03-6.95 (m, 2H), 5.95-5.86 (m, 1H), 5.77-5.69 (m, 1H), 5.29 (s, 1H), 4.08 (s, 1H), 3.94-3.86 (m, 1H), 3.79-3.70 (m, 1H), 3.66 (s, 3H), 3.60 (d, J=14.1 Hz, 1H), 2.70-2.53 (m, 2H), 2.42 (s, 3H), 1.05 (s, 9H). LCMS (m/z) ES+=533 (M+1).

Workup

  1. customthe reaction mixture was partitioned between EtOAc and sat. aq. NaHCO3
  2. washthe organic layer was washed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in THF (0.2 mL)
  7. temperatureheated to 50° C
  8. waitAfter 2 h
  9. extractionextracted with EtOAc
  10. washThe organic layer was washed with brine
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-42caed152aa9485c85c3f6aabc970ee7
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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