Ammonium formate → 5-Ethyl-2-[2-fluoro-4-(3-hydroxy-propylamino)-phenoxy]-phenol

HRID 1023947Notes

Reaction equation

C([O:8][C:9]1[CH:27]=[C:26]([CH2:28][CH3:29])[CH:25]=[CH:24][C:10]=1[O:11][C:12]1[CH:17]=[CH:16][C:15]([NH:18][CH2:19][CH2:20][CH2:21][OH:22])=[CH:14][C:13]=1[F:23])C1C=CC=CC=1.C([O-])=O.[NH4+]>C(O)C.[OH-].[OH-].[Pd+2]>[CH2:28]([C:26]1[CH:25]=[CH:24][C:10]([O:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][CH2:19][CH2:20][CH2:21][OH:22])=[CH:14][C:13]=2[F:23])=[C:9]([OH:8])[CH:27]=1)[CH3:29]

Participants

Conditions

Temperature: 65 °C

Procedure

3-[4-(2-Benzyloxy-4-ethyl-phenoxy)-3-fluoro-phenylamino]-propan-1-ol (400 mg, 1.01 mmol) was taken in 15 ml of absolute ethanol, under nitrogen. To this was added Pd(OH)2, (20%, 50 mg) followed by ammonium formate (200 mg, 3.1 mmol). The reaction mixture was heated at 65° C. and monitored by TLC. After complete consumption of starting material (20 minutes), the heating was stopped and mixture cooled to rt. The reaction mixture was filtered through celite and the residue was washed with methanol. The combined filtrate was concentrated to obtain 300 mg of crude compound showing 70% by HPLC. The crude was purified by preparative HPLC (Column: C18 Symmetry (300×19 mm), 7μ, Mobile phase A: 20 mM ammonium acetate, Mobile phase B: Acetonitrile) to get 140 mg (45.3%) of title compound.

Workup

customAfter complete consumption of starting material (20 minutes)
temperaturemixture cooled to rt
filtrationThe reaction mixture was filtered through celite
washthe residue was washed with methanol
concentrationThe combined filtrate was concentrated
customto obtain 300 mg of crude compound
customThe crude was purified by preparative HPLC (Column: C18 Symmetry (300×19 mm), 7μ, Mobile phase A: 20 mM ammonium acetate, Mobile phase B: Acetonitrile)

Sources & evidence

ORD record: ord-d7cc3cf57c8a49cab9f49add60016609
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08722746B2

Reaction notes

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