Sodium Hydroxide → 4-Bromo-2-nitro-6-tetrahydrofuran-2-yl-aniline

HRID 1404526Notes

Reaction equation

HRID 1404526 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([CH:8]2[CH2:12][CH2:11][CH2:10][O:9]2)[C:5]([NH:13]C(=O)C(F)(F)F)=[C:4]([N+:20]([O-:22])=[O:21])[CH:3]=1.[OH-].[Na+]>O1CCOCC1.CC(OC)(C)C>[Br:1][C:2]1[CH:7]=[C:6]([CH:8]2[CH2:12][CH2:11][CH2:10][O:9]2)[C:5]([NH2:13])=[C:4]([N+:20]([O-:22])=[O:21])[CH:3]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 71551840N-(4-bromo-2-nitro-6-tetrahydrofuran-2-yl-phenyl)-2,2,2-trifluoro-acetamide

Product 1

HCID 681084754-Bromo-2-nitro-6-tetrahydrofuran-2-yl-anilineYield 101.3%

Reagents, catalysts & solvents 2

HCID 15413tert-Butyl methyl etherSolventHCID 312751,4-DioxaneSolvent

Procedure

N-(4-bromo-2-nitro-6-tetrahydrofuran-2-yl-phenyl)-2,2,2-trifluoro-acetamide (6) (54.00 g, 140.9 mmol) was dissolved in 1,4-dioxane (162 mL) and added aqueous 6 M NaOH (70.45 mL, 422.7 mmol, JT-Baker 567202). The reaction mixture was stirred at reflux for 2 days (HPLC showed complete conversion). The mixture was allowed to cool, diluted with MTBE (800 mL), and washed with water (2×200 mL), saturated aqueous NH4Cl, water, and brine. The mixture was dried over MgSO4, filtered, and concentrated under reduced pressure to give (6a) as a dark amber oil (40.96 g, 93% yield; overall 92% HPLC plus NMR purity). LCMS (C18 column eluting with 10-90% MeOH/water gradient from 3-5 minutes with formic acid modifier) M+1: 287.28 (3.44 min). 1H NMR (300 MHz, CDCl3) δ 8.24 (d, J=2.4 Hz, 1H), 7.41 (d, J=2.3 Hz, 1H), 6.91 (s, 2H), 4.80 (t, J=7.2 Hz, 1H), 4.14-4.05 (m, 1H), 3.98-3.90 (m, 1H), 2.36-2.19 (m, 1H), 2.15-2.01 (m, 3H) ppm.

Workup

  1. temperatureat reflux for 2 days (HPLC showed complete conversion)
  2. temperatureto cool
  3. washwashed with water (2×200 mL), saturated aqueous NH4Cl, water, and brine
  4. dry with materialThe mixture was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-411cb70763444c2e9d7d6c3fd04a1d6a
Source dataset
uspto-grants-2014_12
Patent number
US08912326B2

Reaction notes

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