Iodine → Tert-butyl 3-(3-chloro-5-fluorophenyl)-3-hydroxyazetidine-1-carboxylate

HRID 2041896Notes

Reaction equation

HRID 2041896 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([Cl:9])[CH:3]=1.[Mg].II.[C:13]([N:20]1[CH2:23][C:22](=[O:24])[CH2:21]1)([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].[Cl-].[NH4+]>O1CCCC1.C(OCC)C.O>[Cl:9][C:4]1[CH:3]=[C:2]([C:22]2([OH:24])[CH2:21][N:20]([C:13]([O:15][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:14])[CH2:23]2)[CH:7]=[C:6]([F:8])[CH:5]=1

Participants

9

Reactant 5

HCID 807IodineHCID 25517Ammonium ChlorideHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 27362231-Bromo-3-chloro-5-fluorobenzeneHCID 5462224Magnesium

Product 1

HCID 66995489Tert-butyl 3-(3-chloro-5-fluorophenyl)-3-hydroxyazetidine-1-carboxylateYield 70.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-bromo-3-chloro-5-fluorobenzene (1.47 g, 7.01 mmol), magnesium turnings (0.82 g, 31.1 mmol) and a small piece of iodine in dry tetrahydrofuran (50 mL), under nitrogen was gently heated until reaction started and stirred for 1 h at ambient temperature after which a solution of 1-Boc-3-azetidinone (1.0 g, 5.85 mmol) in dry diethyl ether (10 mL) was added dropwise. The resulting mixture was stirred for 15 min and water (70 ml) and saturated aqueous ammonium chloride (20 mL) was added and the mixture was extracted with ethyl acetate (2×50 ml). The combined organic phase was dried (Na2SO4), filtered and evaporated to dryness. The crude product was purified by flash column chromatography on silica gel (ethylacetate/isooctane 1:4 to 1:1) to give the title compound (1.25 g). MS m/z (rel. intensity, 70 eV) 285 (M+, 1), 156 (60), 141 (43), 127 (80), 57 (bp).

Workup

  1. additionwas added dropwise
  2. extractionthe mixture was extracted with ethyl acetate (2×50 ml)
  3. dry with materialThe combined organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe crude product was purified by flash column chromatography on silica gel (ethylacetate/isooctane 1:4 to 1:1)

Sources & evidence

ORD record
ord-742cf429e1b14342ace3d4efc32b66e9
Source dataset
uspto-grants-2013_11
Patent number
US08586572B2

Reaction notes

Loading…