Lithium hydroxide, monohydrate → HCID 118276936, compound

HRID 1053692Notes

Reaction equation

HRID 1053692 reaction equation
[C:1]([O:5][C:6](=[O:29])[CH2:7][CH:8]([C:18]1[CH:19]=[C:20]([CH:25]=[CH:26][C:27]=1[CH3:28])[C:21]([O:23]C)=[O:22])[CH2:9][NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])([CH3:4])([CH3:3])[CH3:2].O.[OH-].[Li+]>O.CO>[C:1]([O:5][C:6](=[O:29])[CH2:7][CH:8]([C:18]1[CH:19]=[C:20]([CH:25]=[CH:26][C:27]=1[CH3:28])[C:21]([OH:23])=[O:22])[CH2:9][NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 118277049HCID 118277049, compound

Product 1

HCID 118276936HCID 118276936, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Adapting a literature known protocol (Dayal, et al., Steroids, 1990, 55(5), 233-237), a reaction mixture of methyl 3-[3-tert-butoxy-1-[(tert-butoxycarbonylamino)methyl]-3-oxo-propyl]-4-methyl-benzoate (8d) (4.08 g, 10.0 mmol) and commercial lithium hydroxide monohydrate (LiOH.H2O) in a mixture of water (20 mL) and methanol (MeOH) (5 mL) is stirred at room temperature. The reaction is monitored by TLC and/or LC/MS to completion. The solvent is partially removed under reduced pressure using a rotary evaporator. The pH of the residue is adjusted to ˜1-2 with a 10.0M hydrochloric acid (HCl). The aqueous phase is extracted with ethyl acetate (4×) and the combined organic extracts are washed with and brine, dried over anhydrous magnesium sulfate (MgSO4), filtered, and the solvents removed under reduced pressure using a rotary evaporator to yield the target compound 3-[3-tert-butoxy-1-[(tert-butoxycarbonylamino)methyl]-3-oxo-propyl]-4-methyl-benzoic acid (8e), which can be used directly in the next step.

Workup

  1. customThe solvent is partially removed under reduced pressure
  2. customa rotary evaporator
  3. extractionThe aqueous phase is extracted with ethyl acetate (4×)
  4. washthe combined organic extracts are washed with and brine
  5. dry with materialdried over anhydrous magnesium sulfate (MgSO4)
  6. filtrationfiltered
  7. customthe solvents removed under reduced pressure
  8. customa rotary evaporator

Sources & evidence

ORD record
ord-94089746863440e08faa4945b6317258
Source dataset
uspto-grants-2016_07
Patent number
US09394236B2

Reaction notes

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