2-Bromo-4-nitrotoluene → N-(2-methyl-5-nitrophenyl)oxetan-3-amine

HRID 627

Reaction equation

HRID 627 reaction equation
Cc1ccc([N+](=O)[O-])cc1Br.Cl.NC1COC1>C1CCCC1.CC(=O)O.CC(=O)O.CC(C1CCCC1P(C1CCCCC1)C1CCCCC1)P(C(C)(C)C)C(C)(C)C.O=C([O-])[O-].[Cs+].[Cs+].[Fe].[Pd]>Cc1ccc([N+](=O)[O-])cc1NC1COC1

Participants

6

Reactant 2

HCID 821892-Bromo-4-nitrotolueneHCID 23062080Oxetan-3-amine hydrochloride

Product 1

HCID 80494079N-(2-methyl-5-nitrophenyl)oxetan-3-amineYield 28.82%

Reagents, catalysts & solvents 3

HCID 10796Cesium carbonateReagentHCID 4144353Palladium (II) acetateCatalystHCID 144543273(R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t-butylphosphine;Ferrocene, 1-[(1R)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(dicyclohexylphosphino)-, (2R)-Catalyst

Conditions

Temperature
90 °C

Procedure

2-bromo-1-methyl-4-nitrobenzene (864 mg, 4mmol), oxetan-3-amine hydrochloride (438 mg, 4 mmol), CS2CO3 (3910 mg, 12.00 mmol), palladium(II) acetate (44.9 mg, 0.20 mmol), (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t- butylphosphine (224 mg, 0.40 mmol) in 1,4-doxane was degased, inflated with Ar and heated at 90 oC for 5h. LCMS showed some product peak. Silica gel 2g was added to the mixture, evaporated all solvents in GeneVac. The sample was dry loaded for purification by ISCO (Hexane/EtOAc=100/10-100/50) N-(2-methyl-5-nitrophenyl)oxetan-3-amine (240 mg, 28.8 %) 1H NMR (400 MHz, CD2Cl2) d: 7.47 (dd, 1H), 7.14 (d, 1H), 6.98 (s, 1H), 4.99 (t, 2H), 4.63 (m, 1H), 4.46 (t, 2H), 4.20(m, 1H), 2.18 (s, 3H). LCMS: 209 [M+H]+.

Sources & evidence

ORD record
ord-85488250153944e595f74578eeba1555
Source dataset
750 AstraZeneca ELN dataset
Original link
View source

Linked notes

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