Hydroxyamine hydrochloride → HCID 87110972, compound

HRID 71225Notes

Reaction equation

HRID 71225 reaction equation
[CH3:1][C:2]1([CH3:19])[O:6][C@H:5]([CH2:7][O:8][C:9]2[C:16]([CH3:17])=[CH:15][C:12]([C:13]#[N:14])=[CH:11][C:10]=2[CH3:18])[CH2:4][O:3]1.Cl.[NH2:21][OH:22].C(=O)(O)[O-].[Na+]>CO>[CH3:1][C:2]1([CH3:19])[O:6][C@H:5]([CH2:7][O:8][C:9]2[C:16]([CH3:17])=[CH:15][C:12](/[C:13](=[N:21]/[OH:22])/[NH2:14])=[CH:11][C:10]=2[CH3:18])[CH2:4][O:3]1

Participants

5

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 66692560(R)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-3,5-dimethylbenzonitrile

Product 1

HCID 87110972HCID 87110972, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

Nitrogen was bubbled in a solution of (R)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-3,5-dimethylbenzonitrile (8.1 g, 31.0 mmol) and hydroxylamine hydrochloride (4.31 g, 62.0 mmol) in MeOH (150 ml) at room temperature (the solution was made in a 500 ml flask w/3 necks fitted with a reflux condenser) for 10 min. To this was then added the sodium bicarbonate (10.42 g, 124 mmol) in one portion. Nitrogen was bubbled for an additional 10 minutes. The reaction mixture was set to stir at 60° C. It was heated for a total of 25 h. The reaction mixture was cooled, concentrated in vacuo and then chromatographed (330 g Redisep cartridge pre-saturated and then eluted with 10% EtOAc-hexanes). 7.29 g (Yield=82%) of the (R,Z)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-N′-hydroxy-3,5-dimethylbenzimidamide was obtained as a white solid. 1H NMR (400 MHz, CCl3D) δ ppm 7.25 (2H, s), 4.80 (3H, br. s.), 4.49 (1H, qd, J=5.93, 5.71 Hz), 4.18 (1H, dd, J=8.35, 6.59 Hz), 3.94 (1H, dd, J=8.35, 5.93 Hz), 3.81-3.88 (1H, m), 3.73-3.80 (1H, m), 2.29 (6H, s), 1.46 (3H, s), 1.40 (3H, s).

Workup

  1. customwas made in a 500 ml flask
  2. customw/3 necks fitted with a reflux condenser) for 10 min
  3. customNitrogen was bubbled for an additional 10 minutes
  4. temperatureIt was heated for a total of 25 h
  5. temperatureThe reaction mixture was cooled
  6. concentrationconcentrated in vacuo
  7. customchromatographed (330 g Redisep cartridge pre-saturated
  8. washeluted with 10% EtOAc-hexanes)

Sources & evidence

ORD record
ord-3c33153e95fb4a328f0983fedb43976b
Source dataset
uspto-grants-2014_09
Patent number
US08822510B2

Reaction notes

Loading…