Hydrochloric Acid → tert-Butyl 3-(4-fluorophenyl)-3-hydroxyazetidine-1-carboxylate

HRID 540371Notes

Reaction equation

HRID 540371 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]Br)=[CH:4][CH:3]=1.[O:10]=[C:11]1[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12]1.[Cl-].[NH4+].Cl>C(OCC)C.C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:11]2([OH:10])[CH2:12][N:13]([C:15]([O:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:16])[CH2:14]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 178418676HCID 178418676, compound

Product 1

HCID 65813955tert-Butyl 3-(4-fluorophenyl)-3-hydroxyazetidine-1-carboxylateYield 43%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

6 ml (11.7 mmol) of a 2M solution of 4-fluorophenylmagnesium bromide in diethyl ether are added dropwise to a solution, immersed in a bath at −50° C., containing 500 mg (2.92 mmol) of 3-oxo-1-(tert-butoxycarbonyl)azetidine in 10 ml of THF. The medium is stirred for 1 hour at −50° C. and hydrolysed by addition of a saturated solution of ammonium chloride. After a return to ambient temperature, a 1N solution of hydrochloric acid is added, followed by extraction with ethyl acetate. The organic phase is dried and evaporated to dryness. The crude product obtained is purified by silica gel chromatography (eluent 7/3 heptane/ethyl acetate). 333 mg in the form of a white powder are obtained with a yield of 43%.

Workup

  1. customimmersed in a bath at −50° C.
  2. extractionfollowed by extraction with ethyl acetate
  3. customThe organic phase is dried
  4. customevaporated to dryness

Sources & evidence

ORD record
ord-ae4e5de8634748f4b13b604fc30b2d11
Source dataset
uspto-grants-2014_10
Patent number
US08871187B2

Reaction notes

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