Sulfuric Acid → Pyridine-2-carboxylic acid [3-(2-chloro-acetylamino)-adamantan-1-yl]amide

HRID 550865Notes

Reaction equation

HRID 550865 reaction equation
[Cl:1][CH2:2][C:3]#[N:4].S(=O)(=O)(O)O.O[C:11]12[CH2:20][CH:15]3[CH2:16][CH:17]([CH2:19][C:13]([NH:21][C:22]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=4)=[O:23])([CH2:14]3)[CH2:12]1)[CH2:18]2.[OH-:30].[Na+]>C(Cl)Cl>[Cl:1][CH2:2][C:3]([NH:4][C:15]12[CH2:20][CH:11]3[CH2:18][CH:17]([CH2:19][C:13]([NH:21][C:22]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=4)=[O:23])([CH2:12]3)[CH2:14]1)[CH2:16]2)=[O:30]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 7856ChloroacetonitrileHCID 14798Sodium HydroxideHCID 59161068Pyridine-2-carboxylic acid (3-hydroxy-adamantan-1-yl)-amide

Product 1

HCID 59161099Pyridine-2-carboxylic acid [3-(2-chloro-acetylamino)-adamantan-1-yl]amideYield 96.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Chloroacetonitrile (2.0 mL, 32 mmol) was cooled to 0° C. Sulfuric acid (1.0 mL, 19 mmol) was added slowly at 0° C. After addition completed, the mixture was stirred at 0° C. for 5 minutes. Pyridine-2-carboxylic acid (3-hydroxy-adamantan-1-yl)-amide (0.42 g, 1.56 mmol, from step 1) was added in one portion and the mixture was stirred at rt overnight. The thick solution was poured into ice-water (10 mL). DCM (10 mL) was added. While the mixture was cooled with an ice-bath, the pH of the aqueous phase (top) was adjusted to 10-13 with 10N ad. NaOH. The aqueous layer was extracted with DCM. The combined organic layer was washed with water and brine, dried over Na2SO4, and concentrated under reduced pressure to afford 0.53 g (96.9%) of crude title compound, pyridine-2-carboxylic acid [3-2-chloro-acetylamino)-adamantan-1-yl]-amide, as an oil, which became a colorless solid upon standing at room temperature. LC-MS (Gradient: acetonitrile in water, 20-85%, in 1.7 minutes with a cycle time of 2 min. Flow rate: 5.0 mL/min. Mobile phase additive: 30 mM of ammonium formate. Column: Inertsil® ODS, 50×4.6 mm, 3 μm particle size (GL Sciences, Tokyo, Japan)): Retention time: 1.08 min; purity (UV254): 100%; ESI-MS m/z: 348 (M+H)+. It was used in the next step without further purification.

Workup

  1. additionAfter addition
  2. stirringthe mixture was stirred at rt overnight
  3. temperatureWhile the mixture was cooled with an ice-bath
  4. extractionThe aqueous layer was extracted with DCM
  5. washThe combined organic layer was washed with water and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-354baebe32c24682adac6240a72dcf36
Source dataset
uspto-grants-2011_05
Patent number
US07947680B2

Reaction notes

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