Sodium Hydroxide → 1,1-dimethylethyl (2R)-2-(3-hydroxy-1-{[(phenylmethyl)oxy]carbonyl}azetidin-3-yl)piperidine-1-carboxylate

HRID 1672928Notes

Reaction equation

HRID 1672928 reaction equation
[C:1]1([CH2:7][O:8][C:9]([N:11]2[CH2:14][C:13]([C@H:31]3[CH2:36][CH2:35][CH2:34][CH2:33][N:32]3[C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])([O:15]C(=O)[C@](OC)(C3C=CC=CC=3)C(F)(F)F)[CH2:12]2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+]>CO>[OH:15][C:13]1([C@H:31]2[CH2:36][CH2:35][CH2:34][CH2:33][N:32]2[C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:12][N:11]([C:9]([O:8][CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[O:10])[CH2:14]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 670515881,1-dimethylethyl (2R)-2-(1-{[(phenylmethyl)oxy]carbonyl}-3-{[(2R)-3,3,3-trifluoro-2-(methyloxy)-2-phenylpropanoyl]oxy}azetidin-3-yl)piperidine-1-carboxylate

Product 1

HCID 670516791,1-dimethylethyl (2R)-2-(3-hydroxy-1-{[(phenylmethyl)oxy]carbonyl}azetidin-3-yl)piperidine-1-carboxylateYield 81%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1,1-Dimethylethyl (2R)-2-(1-{[(phenylmethyl)oxy]carbonyl}-3-{[(2R)-3,3,3-trifluoro-2-(methyloxy)-2-phenylpropanoyl]oxy}azetidin-3-yl)piperidine-1-carboxylate (122.8 mg, 0.21 mmol) was taken into methanol (4 mL) followed by addition of 1M aqueous sodium hydroxide (1 mL) and the resulting solution was stirred for one hour at room temperature. The solution was then partitioned with ethyl acetate and 1N aqueous hydrochloric acid. The organic layer was washed with brine, dried over anhydrous magnesium sulfate then filtered and concentrated. The residue was purified by silica gel flash chromatography using hexanes:ethyl acetate 2:1 to give 1,1-dimethylethyl (2R)-2-(3-hydroxy-1-{[(phenylmethyl)oxy]carbonyl}azetidin-3-yl)piperidine-1-carboxylate (60.8 mg, 81% yield) a colorless amorphous solid. 1,1-dimethylethyl (2S)-2-(3-hydroxy-1-{[(phenylmethyl)oxy]carbonyl}azetidin-3-yl)piperidine-1-carboxylate (87.4 mg, 75% yield) was prepared analogously.

Workup

  1. customThe solution was then partitioned with ethyl acetate and 1N aqueous hydrochloric acid
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationthen filtered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-03ce67d3b60a401d90b1df7fc42295fc
Source dataset
uspto-grants-2011_08
Patent number
US07999006B2

Reaction notes

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