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Tri-o-tolylphosphine → (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-cyano-2,6-dimethylphenyl)propanoate

HRID 534683
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HRID 534683 반응식
Br[C:2]1[C:9]([CH3:10])=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[CH3:11].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH3:34][O:35][C:36](=[O:48])[C@H:37]([CH2:46]I)[NH:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(N(C)C)=O>[CH3:34][O:35][C:36](=[O:48])[C@@H:37]([NH:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:46][C:2]1[C:9]([CH3:10])=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[CH3:11]
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참가 물질

6

반응물 3

HCID 80271Tri-o-tolylphosphineHCID 10903591methyl (2R)-2-(((tert-butoxy)carbonyl)amino)-3-iodopropanoateHCID 110850704-Bromo-3,5-dimethyl-benzonitrile

생성물 1

HCID 46218695(S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-cyano-2,6-dimethylphenyl)propanoate

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium
촉매
HCID 31374Dimethylacetamide용매

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온도
35 °C

실험 절차

A 5 L three-necked round-bottomed flask equipped with a nitrogen inlet, a mechanical stirred, an addition funnel and a thermocouple was charged with 4-bromo-3,5-dimethyl-benzonitrile (210 g, 1.0 mol) and DMAc (750 ml). The resulting suspension was stirred and heated to 35° C. to dissolve the solids. To the resulting mixture was then added P(o-tol)3 (6.0 g, 0.02 mol), Pd2(dba)3 (9.2 g, 0.01 mol) and the resulting mixture heated to about 75-80° C. The cooled mixture prepared in STEP A above was added by cannula to the reaction mixture at a rate which maintained the temperature at about 75-80° C. (about 2 hours). The resulting suspension was cooled to ambient temperature, then aged overnight with moderate agitation. The resulting suspension was then heated to about 35-40° C., filtered with silica (540 g). The silica bed was washed with DMAc (400 mL×2), the combined DMAc solutions cooled to about 0-5° C. and then added slowly to a mixture of ice and deionized water. The resulting mixture was maintained cold for 2 hours, over which time a white solid was observed to precipitate. The resulting mixture was then warmed to ambient temperature and aged overnight. The solid precipitate was cooled by vacuum filtration using a Buchner funnel. The filter cake was rinsed with deionized water (1 L×3), air dried overnight, then dried in a vacuum oven overnight. MeOH (1 L) was added to the solid and the resulting slurry was cooled to about 0-5° C., then aged at this temperature for 1 hour, with stirring. The solid was collected by filtration, washed with cold methanol (400 mL) and dried in a vacuum oven at 45° C. to yield the title compound as an off-white solid.

후처리

  1. customA 5 L three-necked round-bottomed flask equipped with a nitrogen inlet
  2. dissolutionto dissolve the solids
  3. temperaturemaintained the temperature at about 75-80° C. (about 2 hours)
  4. temperatureThe resulting suspension was cooled to ambient temperature
  5. temperatureThe resulting suspension was then heated to about 35-40° C.
  6. filtrationfiltered with silica (540 g)
  7. washThe silica bed was washed with DMAc (400 mL×2)
  8. temperaturethe combined DMAc solutions cooled to about 0-5° C.
  9. additionadded slowly to a mixture of ice
  10. temperatureThe resulting mixture was maintained cold for 2 hours, over which time a white solid
  11. customto precipitate
  12. temperatureThe resulting mixture was then warmed to ambient temperature and aged overnight
  13. temperatureThe solid precipitate was cooled by vacuum filtration
  14. washThe filter cake was rinsed with deionized water (1 L×3), air
  15. customdried overnight
  16. customdried in a vacuum oven overnight
  17. additionMeOH (1 L) was added to the solid
  18. temperaturethe resulting slurry was cooled to about 0-5° C.
  19. waitaged at this temperature for 1 hour
  20. stirringwith stirring
  21. filtrationThe solid was collected by filtration
  22. washwashed with cold methanol (400 mL)
  23. customdried in a vacuum oven at 45° C.

출처 및 근거

ORD 기록
ord-b653d5eccba442bbb9d1440d8d68e07f
출처 데이터셋
uspto-grants-2014_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08853445B2

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