Sodium Cyanide → 4-[(1-Cyanocyclobutyl)amino]-2-fluoro-N-methylbenzamide

HRID 515796Notes

Reaction equation

HRID 515796 reaction equation
[C-:1]#[N:2].[Na+].[NH2:4][C:5]1[CH:14]=[CH:13][C:8]([C:9]([NH:11][CH3:12])=[O:10])=[C:7]([F:15])[CH:6]=1.[C:16]1(=O)[CH2:19][CH2:18][CH2:17]1.[OH-].[Na+]>CC(O)=O.CCO.O>[C:1]([C:16]1([NH:4][C:5]2[CH:14]=[CH:13][C:8]([C:9]([NH:11][CH3:12])=[O:10])=[C:7]([F:15])[CH:6]=2)[CH2:19][CH2:18][CH2:17]1)#[N:2]

Participants

8

Reactant 4

HCID 8929Sodium CyanideHCID 14496CyclobutanoneHCID 14798Sodium HydroxideHCID 441395214-Amino-2-fluoro-N-methylbenzamide

Product 1

HCID 441395204-[(1-Cyanocyclobutyl)amino]-2-fluoro-N-methylbenzamideYield 88.2%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

Sodium cyanide (5.8 g, 119 mmol) was added to a mixture of 4-amino-2-fluoro-N-methylbenzamide (5 g, 29.8 mmol) and cyclobutanone (4.4 mL, 59.5 mmol) in AcOH (90%, 25 mL) and EtOH (25 mL) hooked up to a NaOH scrubber and the resulting mixture was heated to 80° C. overnight. The mixture was cooled to room temperature and poured in water. The yellow precipitate was filtered, washed with water, and dried to afford 6.5 g of 4-((1-cyanocyclobutyl)amino)-2-fluoro-N-methylbenzamide as a pale yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 7.81 (t, 1H), 7.56 (t, 1H), 7.37 (s, 1H), 6.46 (dd, 1H), 6.30 (dd, 1H), 2.80-2.71 (m, 5H), 2.41-2.31 (m, 2H), 2.13-2.00 (m, 2H)

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationThe yellow precipitate was filtered
  3. washwashed with water
  4. customdried

Sources & evidence

ORD record
ord-401d00e2bf0f4d8992aa91374061e99d
Source dataset
uspto-grants-2015_08
Patent number
US09108944B2

Reaction notes

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