Water → HCID 89704786, compound

HRID 928958Notes

Reaction equation

[CH2:1]([O:8][C:9]1[C:10](F)=[C:11]([F:33])[C:12]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[F:32])=[C:13]([CH:24]=1)[C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N-:35]=[N+:36]=[N-:37].[Na+].O>CN(C=O)C>[N:35]([C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:24][C:13]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])=[C:12]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[F:32])[C:11]=1[F:33])=[N+:36]=[N-:37]

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of benzyl 5-benzyloxy-3,4-difluoro-2-((2-fluoro-phenyl)amino)benzoate (21.42 g, 46.26 mmol) in DMF (35 mL) was added NaN3 (3.61 g, 55.51 mmol). The mixture was stirred at 90° C. for 3 h. Then water (300 mL) was added. The solution was extracted with ethyl acetate (150 mL×3). The combined organic extracts were washed with water (100 mL×3) and brine (200 mL) sequentially, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate, 10:1, v/v) and gave the desired product (white solid, 14.63 g, 65% yield). 1H NMR (400 MHz, CDCl3): δ 8.55 (s, 1H), 7.53 (dd, J=8.5, 2.1 Hz, 1H), 7.50-7.33 (m, 10H), 7.09 (m, 1H), 7.05 (m, 1H), 6.90 (m, 1H), 6.83 (m, 1H), 5.35 (s, 2H), 5.20 (s, 2H).

Workup

extractionThe solution was extracted with ethyl acetate (150 mL×3)
washThe combined organic extracts were washed with water (100 mL×3) and brine (200 mL) sequentially
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customThe residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate, 10:1

Sources & evidence

ORD record: ord-7f4c278bc6e54de8a07db4d05409de8e
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290468B2

Reaction notes

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