Toluene → HCID 69811459, compound
Reaction equation
[Br:1][C:2]1[C:3]([F:12])=[C:4]([C:8]([F:11])=[CH:9][CH:10]=1)C(O)=O.C1(C)C=CC=CC=1.CC[N:22]([CH:26](C)C)C(C)C.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:36])=CC=1.[CH3:46][C:47]([OH:50])([CH3:49])[CH3:48]>>[Br:1][C:2]1[C:3]([F:12])=[C:4]([NH:22][C:26](=[O:36])[O:50][C:47]([CH3:49])([CH3:48])[CH3:46])[C:8]([F:11])=[CH:9][CH:10]=1Participants
Conditions
- Temperature
- 111 °C
Procedure
To a round bottom flask containing 3-bromo-2,6-difluorobenzoic acid (5 g, 21.1 mmol) under nitrogen with a condenser was added toluene (35 mL) and t-BuOH (35 mL). To this solution was added DIEA (4.4 ml, 25.3 mmol) and DPPA (5.7 mL, 26.4 mmol). The reaction mixture was heated to 111° C. in an oil bath for 48 hours. The reaction was allowed to cool to room temperature and the volatiles were removed in vacuo. The resulting residue was suspended with water and extracted with EtOAc. The organic phase was washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica. Purification by flash chromatography (SiO2; 0-100% EtOAc in heptane) afforded 3.49 g (54%) of tert-butyl 3-bromo-2,6-difluorophenylcarbamate: 1H NMR (400 MHz, DMSO-d6) δ 1.34-1.54 (m, 9H) 7.17 (m, 1H) 7.63 (ddd, J=8.9, 7.9, 5.9 Hz, 1H).
Workup
- temperatureto cool to room temperature
- customthe volatiles were removed in vacuo
- extractionextracted with EtOAc
- washThe organic phase was washed with water, brine
- dry with materialdried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated onto silica
- customPurification by flash chromatography (SiO2; 0-100% EtOAc in heptane)
Sources & evidence
- ORD record
- ord-d2057e6da2f14028bb91336912451e14
- Source dataset
- uspto-grants-2012_08
- Patent number
- US08242260B2
Reaction notes
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