Diisopropylethylamine → (5-Amino-4-fluoro-2-methyl-phenyl)-carbamic acid 2-trimethylsilanyl-ethyl ester

HRID 724434Notes

Reaction equation

[CH3:1][Si:2]([CH3:19])([CH3:18])[CH2:3][CH2:4][O:5][C:6](=O)[O:7]C1C=CC([N+]([O-])=O)=CC=1.CCN(C(C)C)C(C)C.[F:29][C:30]1[CH:35]=[C:34]([CH3:36])[C:33]([NH2:37])=[CH:32][C:31]=1[NH2:38]>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH3:1][Si:2]([CH3:19])([CH3:18])[CH2:3][CH2:4][O:5][C:6](=[O:7])[NH:37][C:33]1[CH:32]=[C:31]([NH2:38])[C:30]([F:29])=[CH:35][C:34]=1[CH3:36]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of carbonic acid 4-nitro-phenyl ester 2-trimethylsilanyl-ethyl ester (566 mg, 2 mmol) in DMF (4 ml) at 23° C. under an atmosphere of argon was added DMAP (12 mg, 0.1 mmol), DIEA (0.35 ml, 2 mmol) and 4-fluoro-6-methyl-benzene-1,3-diamine. The resulting solution was heated to 50° C. for 48 h. The reaction mixture was quenched with saturated NaHCO3 (aq), extracted with EtOAc (3×20 ml). The EtOAc was removed in-vacuo, and the residue was re-dissolved in Et2O then washed with 3 N NaOH (aq), water, brine, dried with Na2SO4, filtered and concentrated. Purification by silica gel chromatography (2:8-7:3 ethyl acetate-hexane) gave (5-amino-4-fluoro-2-methyl-phenyl)-carbamic acid 2-trimethylsilanyl-ethyl ester (160 mg, 28%). MS (ESI+) [M+H]/z Calc'd 634. found 634.

Workup

customThe reaction mixture was quenched with saturated NaHCO3 (aq)
extractionextracted with EtOAc (3×20 ml)
customThe EtOAc was removed in-vacuo
dissolutionthe residue was re-dissolved in Et2O
washthen washed with 3 N NaOH (aq), water, brine
dry with materialdried with Na2SO4
filtrationfiltered
concentrationconcentrated
customPurification by silica gel chromatography (2:8-7:3 ethyl acetate-hexane)

Sources & evidence

ORD record: ord-f7e82eda7f364cfcb7150b550d34f288
Source dataset: uspto-grants-2006_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07141587B2

Reaction notes

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