tert-Butanol → Tert-butyl 3-bromo-2-fluoro-5-methylphenylcarbamate

HRID 885735Notes

Reaction equation

[Br:1][C:2]1[C:3]([F:12])=[C:4]([CH:8]=[C:9]([CH3:11])[CH:10]=1)C(O)=O.CC[N:15]([CH:19](C)C)C(C)C.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:29])=CC=1.[CH3:39][C:40]([OH:43])([CH3:42])[CH3:41]>C1(C)C=CC=CC=1>[Br:1][C:2]1[C:3]([F:12])=[C:4]([NH:15][C:19](=[O:29])[O:43][C:40]([CH3:42])([CH3:41])[CH3:39])[CH:8]=[C:9]([CH3:11])[CH:10]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of 3-bromo-2-fluoro-5-methylbenzoic acid (2.1 g, 9.01 mmol) in toluene (30 mL) and t-BuOH (15 mL), DIEA (1.9 mL, 10.8 mmol) and DPPA (2.4 mL, 11.3 mmol) were added and the reaction mixture was heated to and maintained at 120° C. for 24 hours. The reaction was allowed to cool to room temperature and concentrated to afford a brown oil. The oil was partitioned between diethyl ether and water and the resulting layers separated. The diethyl ether layer was washed with water, brine, dried (MgSO4) and concentrated. Purification by flash chromatography (SiO2, 0-5% EtOAc in heptane) provided tert-butyl 3-bromo-2-fluoro-5-methylphenylcarbamate (985 mg, 3.2 mmol, 36%) as a clear pale yellow oil: LCMS(m/z) 247.9 (MH+-t-butyl); tR=1.14 minutes; 1H NMR (300 MHz, CDCl3) δ 1.53 (s, 9H) 2.29 (s, 3H) 6.67 (br s, 1H) 6.98 (d, J=6.2 Hz, 1H) 7.88 (d, J=6.5 Hz, 1H).

Workup

temperaturethe reaction mixture was heated to and
temperatureto cool to room temperature
concentrationconcentrated
customto afford a brown oil
customThe oil was partitioned between diethyl ether and water
customthe resulting layers separated
washThe diethyl ether layer was washed with water, brine
dry with materialdried (MgSO4)
concentrationconcentrated
customPurification by flash chromatography (SiO2, 0-5% EtOAc in heptane)

Sources & evidence

ORD record: ord-7b13df1d23eb44a3b4884548c888d7bd
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08242260B2

Reaction notes

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