Ammonium Chloride → 1,1-Dimethylethyl 3-(3,4-difluorophenyl)-3-hydroxy-1-azetidinecarboxylate

HRID 2041893Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[C:4]([F:9])[CH:3]=1.C([Li])CCCCC.[C:17]([N:24]1[CH2:27][C:26](=[O:28])[CH-:25]1)([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].[Cl-].[NH4+]>C(OCC)C>[F:9][C:4]1[CH:3]=[C:2]([C:26]2([OH:28])[CH2:25][N:24]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH2:27]2)[CH:7]=[CH:6][C:5]=1[F:8]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 4-bromo-1,2-difluorobenzene (1.35 g, 7.01 mmol) in dry diethylether (50 ml) at −78° C. under nitrogen was added n-hexyllithium (2.3 M in hexane, 3.0 ml, 7.01 mmol) dropwise. The mixture was stirred for 10 min after which a solution of 1-Boc-azetidone (1.0 g, 5.85 mmol) in dry diethyl ether (10 mL) was added dropwise. The resulting mixture was stirred at −78° C. for 10 min and then brought to ambient temperature and stirred for 10 min. Saturated aqueous ammonium chloride (50 mL,) was added and the mixture was extracted with tert-butyl methyl ether (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 1:1) to give the title compound (1.06 g). MS m/z (rel. intensity, 70 eV) 285 (M+, 1), 156 (60), 141 (43), 127 (80), 57 (bp).

Workup

additionwas added dropwise
custombrought to ambient temperature
stirringstirred for 10 min
extractionthe mixture was extracted with tert-butyl methyl ether (2×50 ml)
dry with materialThe combined organic phase was dried (Na2SO4)
filtrationfiltered
customevaporated to dryness
customThe crude product was purified by flash column chromatography on silica gel (ethylacetate/isooctane 1:1)

Sources & evidence

ORD record: ord-b29ed858a8e24bad9e9c050329f81af6
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08586572B2

Reaction notes

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