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Dimethoxymethane → (R)-tert-Butyl 1-(3-benzyl-7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methylpropylcarbamate

HRID 1373370
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HRID 1373370 반응식
[C:1]([O:5][C:6](=[O:31])[NH:7][C@@H:8]([CH:12]=[N:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[C:21](=[O:30])[NH:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH:9]([CH3:11])[CH3:10])([CH3:4])([CH3:3])[CH3:2].COCOC.C[Si](N[Si](C)(C)C)(C)C>O>[C:1]([O:5][C:6](=[O:31])[NH:7][C@@H:8]([C:12]1[N:22]([CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:21](=[O:30])[C:15]2[C:14](=[CH:19][C:18]([Cl:20])=[CH:17][CH:16]=2)[N:13]=1)[CH:9]([CH3:11])[CH3:10])([CH3:3])([CH3:4])[CH3:2]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 8020DimethoxymethaneHCID 13838HexamethyldisilazaneHCID 69519159(R)-{1-[(2-benzylcarbamoyl-5-chloro-phenylimino)-methyl]-2-methyl-propyl}-carbamic acid tert-butyl ester

생성물 1

HCID 57351218(R)-tert-Butyl 1-(3-benzyl-7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methylpropylcarbamate수율 51%

시약·촉매·용매 1

HCID 962
Water
용매

실험 절차

A dry 3-necked, round bottomed flask, equipped with a magnetic stirrer, gas bubbler, heating mantle and a water condenser, was charged with 545.73 g (1.19 mol) of (R)-{1-[(2-benzylcarbamoyl-5-chloro-phenylimino)-methyl]-2-methyl-propyl}-carbamic acid tert-butyl ester (a compound of Formula 106, obtained, for example, as described in Example 2.3), 520 mL of dimethoxymethane and 520 mL (2.492 mol) of HMDS. The mixture was heated to reflux for 24 hours and then allowed to cool. The volatiles were removed by rotary evaporation, leaving an oily residue that was then triturated with ethanol (3×125 mL) to remove residual HMDS or ammonia. To the resulting oil was added 400 mL of ethanol, and the mixture was heated until a homogeneous solution had been obtained. At refulx temperature, 60 mL of water was added and the solution was allowed to cool slowly with light stirring, overnight. The resulting white suspension was allowed to settle; an aliquot of the supernatant was removed and treated dropwise with water to confirm completion (no more solid was formed). The solid was filtered, washed (3×200 mL H2O/EtOH (1:4)), and dried in an oven at 50° C. for 48 hours to afford 260.23 g (51% yield) of the enantiomerically pure title compound of Formula 107, (R)-[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methylpropyl]-carbamic acid tert-butyl ester.

후처리

  1. customA dry 3-necked, round bottomed flask, equipped with a magnetic stirrer
  2. temperaturegas bubbler, heating mantle and a water condenser
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 24 hours
  5. temperatureto cool
  6. customThe volatiles were removed by rotary evaporation
  7. customleaving an oily residue that
  8. customwas then triturated with ethanol (3×125 mL)
  9. customto remove residual HMDS or ammonia
  10. additionTo the resulting oil was added 400 mL of ethanol
  11. temperaturethe mixture was heated until a homogeneous solution
  12. customhad been obtained
  13. temperatureto cool slowly with light stirring, overnight
  14. customan aliquot of the supernatant was removed
  15. additiontreated dropwise with water
  16. customwas formed)
  17. filtrationThe solid was filtered
  18. washwashed (3×200 mL H2O/EtOH (1:4))
  19. customdried in an oven at 50° C. for 48 hours

출처 및 근거

ORD 기록
ord-e80ef0c021d246b9bb3f1bd55fc9247e
출처 데이터셋
uspto-grants-2007_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07161002B2

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