Sodium Cyanide → HCID 67375081, compound

HRID 515794Notes

Reaction equation

HRID 515794 reaction equation
[C-:1]#[N:2].[Na+].[NH2:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[C:7]([F:12])[CH:6]=1.[C:13]1(=O)[CH2:16][CH2:15][CH2:14]1.[OH-].[Na+]>C(O)(=O)C.O>[F:12][C:7]1[CH:6]=[C:5]([NH:4][C:13]2([C:1]#[N:2])[CH2:16][CH2:15][CH2:14]2)[CH:10]=[CH:9][C:8]=1[OH:11]

Participants

7

Reactant 4

HCID 8929Sodium CyanideHCID 14496CyclobutanoneHCID 14798Sodium HydroxideHCID 2735918Phenol, 4-amino-2-fluoro-

Product 1

HCID 67375081HCID 67375081, compoundYield 68.7%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

Sodium cyanide (2.5 g, 50.8 mmol) was added to a mixture of 4-amino-2-fluorophenol (4.3 g, 33.9 mmol) and cyclobutanone (3.8 mL, 50.8 mmol) in acetic acid (99%, 30 mL) hooked up to a NaOH scrubber and the resulting mixture was stirred at room temperature for 6 h. The mixture was poured in water and the aqueous layer was extracted with EtOAc (3×). The organics were combined, washed with a saturated solution of sodium bicarbonate (4×), dried over sodium sulfate, and evaporated to dryness. The residue was purified by column chromatography on silica gel eluting with 0 to 50% EtOAc/hexanes to afford 4.8 g of 1-((3-fluoro-4-hydroxyphenyl)amino)cyclobutanecarbonitrile as a beige solid. 1H NMR (300 MHz, DMSO-d6) δ 8.98 (s, 1H), 6.80 (t, 1H), 6.36 (dd, 1H), 6.28 (m, 2H), 2.71-2.62 (m, 2H), 2.35-2.25 (m, 2H), 2.12-2.00 (m, 2H).

Workup

  1. extractionthe aqueous layer was extracted with EtOAc (3×)
  2. washwashed with a saturated solution of sodium bicarbonate (4×)
  3. dry with materialdried over sodium sulfate
  4. customevaporated to dryness
  5. customThe residue was purified by column chromatography on silica gel eluting with 0 to 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-39aaeb13019d4abcbb6b26dbe62b5d9a
Source dataset
uspto-grants-2015_08
Patent number
US09108944B2

Reaction notes

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