Hydrochloric Acid → HCID 118045321, compound

HRID 2284875Notes

Reaction equation

HRID 2284875 reaction equation
O.O.O.O.O.O.O.[Cl-].[Ce+3].[Cl-].[Cl-].[C:12]([O:15][CH2:16][C@@H:17]1[C@@H:22]([O:23][C:24](=[O:26])[CH3:25])[C@H:21]([O:27][C:28](=[O:30])[CH3:29])[C@@H:20]([O:31][C:32](=[O:34])[CH3:33])[C@H:19]([N:35]2[C:43]3[C:38](=[C:39]([CH3:44])[CH:40]=[CH:41][CH:42]=3)[C:37]([C:45](=[O:60])[C:46]3[CH:51]=[CH:50][C:49]([O:52][CH2:53][C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)=[CH:48][CH:47]=3)=[CH:36]2)[O:18]1)(=[O:14])[CH3:13].[BH4-].[Na+].Cl>C(O)C.O.CC(OC)(C)C.O1CCCC1>[C:12]([O:15][CH2:16][C@@H:17]1[C@@H:22]([O:23][C:24](=[O:26])[CH3:25])[C@H:21]([O:27][C:28](=[O:30])[CH3:29])[C@@H:20]([O:31][C:32](=[O:34])[CH3:33])[C@H:19]([N:35]2[C:43]3[C:38](=[C:39]([CH3:44])[CH:40]=[CH:41][CH:42]=3)[C:37]([CH:45]([C:46]3[CH:47]=[CH:48][C:49]([O:52][CH2:53][C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)=[CH:50][CH:51]=3)[OH:60])=[CH:36]2)[O:18]1)(=[O:14])[CH3:13]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydride3×HCID 21585214Cerium trichloride heptahydrateHCID 118045092HCID 118045092, compound

Product 1

HCID 118045321HCID 118045321, compoundYield 100%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

To a temperature controlled stirred reactor charge cerium (III) chloride heptahydrate (4.55 moles; 1.12 kg) in ethanol (4.96 L) and stir to give a solution. Add [(2R,3R,4S,5R,6R)-3,4,5-triacetoxy-6-[3-(4-benzyloxybenzoyl)-4-methyl-indol-1-yl]tetrahydropyran-2-yl]methyl acetate (1.52 moles; 1.38 kg) and tetrahydrofuran (7.57 L). Cool the mixture to +2° C. and add sodium tetrahydroborate (4.55 moles; 172.18 g) in portions over 3 hours maintaining the internal temperature between 0 and +5° C. during addition. When the addition is complete, stir the mixture at 5° C. for 1 hour. Add further sodium tetrahydroborate (687.24 mmoles; 26.00 g) and stir the mixture for 30 minutes. Add additional sodium tetrahydroborate (0.45 equiv; 687.24 mmoles; 26.00 g) and stir the mixture overnight. Pour the mixture into MTBE (5 L) and water (10 L). Slowly add hydrochloric acid (2 N) with stirring until mixture is slightly acidic to pH paper. Separate the organic layer, wash with brine, dry over MgSO4, filter, and concentrate under reduced pressure to afford the title compound in acceptable purity for use in the next step (1547 g; assumed 66% purity and 100% yield for the purposes of calculation in the next reaction) mass spectrum (m/z): 656.4 (M+1-18).

Workup

  1. stirringstir
  2. customto give a solution
  3. temperatureCool the mixture to +2° C.
  4. temperaturemaintaining the internal temperature between 0 and +5° C.
  5. additionduring addition
  6. additionWhen the addition
  7. stirringstir the mixture at 5° C. for 1 hour
  8. stirringstir the mixture for 30 minutes
  9. stirringstir the mixture overnight
  10. customSeparate the organic layer
  11. washwash with brine
  12. dry with materialdry over MgSO4
  13. filtrationfilter
  14. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-9e98a0a121db458f96513ba7e390669a
Source dataset
uspto-grants-2015_09
Patent number
US09145437B2

Reaction notes

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