Methanol → HCID 118045109, compound

HRID 2284877Notes

Reaction equation

HRID 2284877 reaction equation
[C:1]([O:4][CH2:5][C@@H:6]1[C@@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:10]([O:16][C:17](=[O:19])[CH3:18])[C@@H:9]([O:20][C:21](=[O:23])[CH3:22])[C@H:8]([N:24]2[C:32]3[C:27](=[C:28]([CH3:33])[CH:29]=[CH:30][CH:31]=3)[C:26]([CH2:34][C:35]3[CH:40]=[CH:39][C:38]([O:41]CC4C=CC=CC=4)=[CH:37][CH:36]=3)=[CH:25]2)[O:7]1)(=[O:3])[CH3:2].CO.O1CCCC1.C([O-])=O.[NH4+]>>[C:1]([O:4][CH2:5][C@@H:6]1[C@@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:10]([O:16][C:17](=[O:19])[CH3:18])[C@@H:9]([O:20][C:21](=[O:23])[CH3:22])[C@H:8]([N:24]2[C:32]3[C:27](=[C:28]([CH3:33])[CH:29]=[CH:30][CH:31]=3)[C:26]([CH2:34][C:35]3[CH:40]=[CH:39][C:38]([OH:41])=[CH:37][CH:36]=3)=[CH:25]2)[O:7]1)(=[O:3])[CH3:2]

Participants

5

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 2723923Ammonium formateHCID 118045163HCID 118045163, compound

Product 1

HCID 118045109HCID 118045109, compoundYield 99.7%

Conditions

Temperature
40 °C

Procedure

To a mixture of [(2R,3R,4S,5R,6R)-3,4,5-triacetoxy-6-[3-[(4-benzyloxyphenyl)methyl]-4-methyl-indol-1-yl]tetrahydropyran-2-yl]methyl acetate (1.00 equiv; 1.05 moles; 692.80 g), methanol (85.59 moles; 3.46 L; 2.74 kg), and tetrahydrofuran (42.57 moles; 3.46 L; 3.07 kg) add ammonium formate (5.27 moles; 332.10 g). Purge the reaction vessel with nitrigen and add 5% palladium on charcoal (69.30 g; Johnson Matthey type 87 L, 57.8% moisture content) as a slurry in isopropyl alcohol. Heat the mixture at 38-42° C. for 15 mins (moderate bubbling observed). Remove the heating bath and stir the reaction mixture for 15 minutes whilst cooling. Filter the mixture through diatomaceous earth and concentrate the filtrate under reduced pressure. Partition the residue between ethyl acetate (7.5 L) and water (1 L). Separate the organic layer and wash with brine then dry over MgSO4. Filter, and concentrate under reduced pressure to give the title compound (594 g; 99% yield) mass spectrum (m/z): 568.2 (M+1) and 590.2 (M+23).

Workup

  1. customPurge the reaction vessel with nitrigen
  2. additionadd 5% palladium on charcoal (69.30 g; Johnson Matthey type 87 L, 57.8% moisture content) as a slurry in isopropyl alcohol
  3. custom(moderate bubbling observed)
  4. customRemove the heating bath
  5. temperaturewhilst cooling
  6. filtrationFilter the mixture through diatomaceous earth
  7. concentrationconcentrate the filtrate under reduced pressure
  8. customPartition the residue between ethyl acetate (7.5 L) and water (1 L)
  9. customSeparate the organic layer
  10. washwash with brine
  11. dry with materialthen dry over MgSO4
  12. filtrationFilter
  13. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-4178d515448446eeab53cfabd46d1286
Source dataset
uspto-grants-2015_09
Patent number
US09145437B2

Reaction notes

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