Hydrochloric Acid → (R)-[1-(7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methylpropyl]-carbamic acid tert-butyl ester

HRID 1373373Notes

Reaction equation

HRID 1373373 reaction equation
C1COCC1.[C:6]([O:10][C:11](=[O:29])[NH:12][C@@H:13]([CH:17]=[N:18][C:19]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=1[C:26](=[O:28])[NH2:27])[CH:14]([CH3:16])[CH3:15])([CH3:9])([CH3:8])[CH3:7].O.[OH-].[Li+].Cl>O>[C:6]([O:10][C:11](=[O:29])[NH:12][C@@H:13]([C:17]1[NH:27][C:26](=[O:28])[C:20]2[C:19](=[CH:24][C:23]([Cl:25])=[CH:22][CH:21]=2)[N:18]=1)[CH:14]([CH3:16])[CH3:15])([CH3:8])([CH3:9])[CH3:7]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 69518186(R)-{1-[(2-carbamoyl-5-chloro-phenylimino)-methyl]-2-methyl-propyl}-carbamic acid tert-butyl ester

Product 1

HCID 136376397(R)-[1-(7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methylpropyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A dry 3-necked, round bottomed flask, equipped with a magnetic stirrer, nitrogen inlet, heating mantle, and a water condenser, is charged with 60 mL of THF, 3.70 g (10 mmol) of (R)-{1[(2-carbamoyl-5-chloro-phenylimino)-methyl]-2-methyl-propyl}-carbamic acid tert-butyl ester (the compound of Formula 201 prepared, e.g., as described in Example 6.1), and 0.46 g (11 mmol) of lithium hydroxide monohydrate. The mixture is heated to reflux and the reaction monitored by TLC (hexanes/ethyl acetate 7:3) by which, after 1 h of refluxing, the reaction is shown to be complete. The mixture is allowed to cool to room temperature and transferred to a round bottom 1-necked flask followed by dilution with 60 mL of water. The stirring mixture is then slowly acidified to pH=5 by adding 1N hydrochloric acid and the THF is removed by rotary evaporation. The white suspension is separated by filtration and dried in high vacuum to afford the title compound of Formula 202, (R)-[1-(7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methylpropyl]-carbamic acid tert-butyl ester.

Workup

  1. customA dry 3-necked, round bottomed flask, equipped with a magnetic stirrer, nitrogen inlet
  2. temperatureheating mantle
  3. customprepared
  4. temperatureThe mixture is heated
  5. temperatureto reflux
  6. temperatureof refluxing
  7. customtransferred to a round bottom 1-necked flask
  8. customthe THF is removed by rotary evaporation
  9. customThe white suspension is separated by filtration
  10. customdried in high vacuum

Sources & evidence

ORD record
ord-d5808baf4f4a4c7eab3e65df070a6535
Source dataset
uspto-grants-2007_01
Patent number
US07161002B2

Reaction notes

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