Aluminium lithium hydride → {(S)-3-[3-(4-chlorophenoxy)-azetidin-1-yl]-1-hydroxymethyl-propyl}-carbamic acid tert-butyl ester

HRID 1182102Notes

Reaction equation

HRID 1182102 reaction equation
C([O:8][C:9](=O)[C@@H:10]([NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:11][C:12]([N:14]1[CH2:17][CH:16]([O:18][C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[CH2:15]1)=O)C1C=CC=CC=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[C:30]([O:29][C:27](=[O:28])[NH:26][C@H:10]([CH2:9][OH:8])[CH2:11][CH2:12][N:14]1[CH2:15][CH:16]([O:18][C:19]2[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=2)[CH2:17]1)([CH3:31])([CH3:33])[CH3:32]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 69409254(S)-2-tert-butoxycarbonylamino-4-[3-(4-chloro-phenoxy)-azetidin-1-yl]4-oxo-butyric acid benzyl ester

Product 1

HCID 69410725{(S)-3-[3-(4-chlorophenoxy)-azetidin-1-yl]-1-hydroxymethyl-propyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)-2-tert-butoxycarbonylamino-4-[3-(4-chloro-phenoxy)-azetidin-1-yl]4-oxo-butyric acid benzyl ester (1.0 g, 2.04 mmol) in dry THF (10 ml) is treated with a 1M solution of lithium aluminium hydride (5.1 ml) keeping the temperature between 20-30° C. using an ice-water bath. The reaction mixture is stirred at ambient temperature under argon for 2 hours, then quenched by addition of saturated aqueous Na2SO4 and filtered through a celite™ filter. The filtrate is partitioned between ethylacetate and saturated brine. The ethylacetate phase dried over MgSO4 and evaporated. The crude product is purified by flash silica chromatography (elution with 5:95 methanol/dichloromethane) to afford {(S)-3-[3-(4-chloro-phenoxy)-azetidin-1-yl]-1-hydroxymethyl-propyl}-carbamic acid tert-butyl ester. [MH]+ 371.0.

Workup

  1. custombetween 20-30° C.
  2. customquenched by addition of saturated aqueous Na2SO4
  3. filtrationfiltered through a celite™
  4. filtrationfilter
  5. customThe filtrate is partitioned between ethylacetate and saturated brine
  6. dry with materialThe ethylacetate phase dried over MgSO4
  7. customevaporated
  8. customThe crude product is purified by flash silica chromatography (elution with 5:95 methanol/dichloromethane)

Sources & evidence

ORD record
ord-aced7d86659d4573917599e4095cda85
Source dataset
uspto-grants-2007_10
Patent number
US07288537B2

Reaction notes

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