Isopropyl Acetate → HCID 131731247, compound

HRID 1188307Notes

Reaction equation

HRID 1188307 reaction equation
[Li+].[BH4-].[OH-].[Na+].C(OC(C)C)(=O)C.[CH3:12][C:13]1([CH3:26])[C@:17]2([CH2:21][S:22]([OH:25])(=[O:24])=[O:23])[C:18]([CH2:20][CH:14]1[CH2:15][CH2:16]2)=[O:19].[N:27]1(O)CCCCC1>C1COCC1.CC(O)C.C(O)C>[CH3:13][C@H:14]1[NH:27][CH2:21][C@H:17]([CH2:18][OH:19])[CH2:16][CH2:15]1.[CH3:12][C:13]1([CH3:26])[C:17]2([CH2:21][S:22]([OH:25])(=[O:24])=[O:23])[C:18]([CH2:20][CH:14]1[CH2:15][CH2:16]2)=[O:19]

Participants

9

Reactant 5

HCID 7915Isopropyl AcetateHCID 14798Sodium HydroxideHCID 209351-HydroxypiperidineHCID 218580(1S)-(+)-Camphor-10-sulphonic acidHCID 4148881Lithium borohydride

Product 1

HCID 131731247HCID 131731247, compoundYield 47%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
0 °C

Procedure

Crude A-2 (40 g assay; 55.94 g total) was dissolved in THF (773 mL). Ethanol (43.1 g) was added to the solution and the solution cooled to 0° C. LiBH4 (228 ml; 4.1M in THF) was added over 30 minutes at below 5° C. and mixture was stirred at RT. Mixture was warmed to 20° C. and stirred overnight. The reaction mixture was cooled to 10° C. and added 6M HCL (240 mL) with care over 30 minutes. The white cloudy mixture was stirred at 20° C. for 2 hours. pH of mixture: pH=1. The pH of the reaction mixture was adjusted to pH 12-14 by the addition of 10 M NaOH (120 mL) and isopropyl acetate (120 mL) added. The layers were separated and the aqueous layer re-extracted with isopropyl acetate (2×240 mL). The organic layers were combined and evaporated to residue. The oily residue was flushed with isopropanol (3×200 mL) to give a water content of <200 μL/mL. The crude oil was then dissolved in THF (450 mL). Solvent analysis gave no IPAc present, <1% IPA present. A solution of D-(+)-camphorsulfonic acid (54.3 g) in THF (130 mL) was added over 30 minutes to the THF solution of the piperidinol. A white solid crystallized. The mixture was stirred at 20° C. overnight. The slurry was diluted with MTBE (300 mL) and the mixture was cooled to 0° C. for 2 hours before filtering. The solid was washed with 1:1 THF:MTBE (100 mL) and MTBE (100 mL). The solid was dried in vacuo at 45° C. overnight to give A-5 as a white solid (39.7 g) in 47% yield, diastereomer ratio: 20:1 trans:cis (NMR)

Workup

  1. temperatureMixture was warmed to 20° C.
  2. stirringstirred overnight
  3. temperatureThe reaction mixture was cooled to 10° C.
  4. additionadded 6M HCL (240 mL) with care over 30 minutes
  5. stirringThe white cloudy mixture was stirred at 20° C. for 2 hours
  6. additionadded
  7. customThe layers were separated
  8. extractionthe aqueous layer re-extracted with isopropyl acetate (2×240 mL)
  9. customevaporated to residue
  10. customThe oily residue was flushed with isopropanol (3×200 mL)
  11. customto give a water content of <200 μL/mL
  12. customSolvent analysis gave no IPAc present
  13. customA white solid crystallized
  14. stirringThe mixture was stirred at 20° C. overnight
  15. additionThe slurry was diluted with MTBE (300 mL)
  16. temperaturethe mixture was cooled to 0° C. for 2 hours
  17. filtrationbefore filtering
  18. washThe solid was washed with 1:1 THF
  19. customThe solid was dried in vacuo at 45° C. overnight

Sources & evidence

ORD record
ord-733dc6e8d4434af7915ec8e6c08c7c57
Source dataset
uspto-grants-2014_03
Patent number
US08674093B2

Reaction notes

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