Sulfuric Acid → Ethyl-5-(4-[2-fluorobenzyloxy]phenyl)-3,4-dihydro-2H-pyrrole-2-carboxyate

HRID 410003노트

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HRID 410003 반응식
[F:1][C:2]1[CH:19]=[CH:18][CH:17]=[CH:16][C:3]=1[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12](=O)[CH:13]=[CH2:14])=[CH:8][CH:7]=1.C1(C(C2C=CC=CC=2)=[N:27][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])C=CC=CC=1.OS(O)(=O)=O.C([O-])(O)=O.[Na+]>C1COCC1.CC([C@@H]1N=C([C]2[C](P(C3C=CC=CC=3)C3C=CC=CC=3)[CH][CH][CH]2)OC1)C.[CH]1[CH][CH][CH][CH]1.[Fe].C1CCN2C(=NCCC2)CC1>[CH2:32]([O:31][C:29]([CH:28]1[CH2:14][CH2:13][C:12]([C:9]2[CH:10]=[CH:11][C:6]([O:5][CH2:4][C:3]3[CH:16]=[CH:17][CH:18]=[CH:19][C:2]=3[F:1])=[CH:7][CH:8]=2)=[N:27]1)=[O:30])[CH3:33]

참가 물질

8

반응물 4

HCID 1118Sulfuric AcidHCID 319508Ethyl 2-(diphenylmethyleneamino)acetateHCID 516892Sodium BicarbonateHCID 533483441-(4-[2-Fluorobenzyloxy]phenyl)-2-propen-1-one

생성물 1

HCID 53348357Ethyl-5-(4-[2-fluorobenzyloxy]phenyl)-3,4-dihydro-2H-pyrrole-2-carboxyate수율 84%

시약·촉매·용매 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene촉매HCID 72376438(2R)-1-[(4S)-4,5-Dihydro-4-(1-methylethyl)-2-oxazolyl]-2-(diphenylphosphino)ferrocene촉매HCID 8028Tetrahydrofuran용매2회

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온도
22.5 °C

실험 절차

(S)-4-Isopropyl-2-[(S)-2-(diphenylphosphino)ferrocen-1-yl]oxazoline (18.8 mg, 0.039 mmol) and Cu(MeCN)4PF6 (14.5 mg, 0.039 mmol) were added to a dried, nitrogen swept reaction vessel. Anhydrous, degassed, BHT inhibited THF (5.0 mL) was then added and the mixture was stirred for 30 minutes at 20-25° C. The resulting solution was then cooled to −78° C. and a solution of 1-(4-[2-fluorobenzyloxy]phenyl)-2-propen-1-one (P4, 2.0 g, 7.80 mmol) and ethyl N-(diphenylmethylidene)glycinate (2.29 g, 8.58 mmol) in THF (15 mL total volume) was added over 1-2 minutes. After 3-5 minutes, a solution of DBU (5.9 mg, 0.039 mmol) in THF (0.5 mL total volume) was added. The solution was then stirred for 8-12 hours at −78° C. The reaction mixture was then warmed to 0-5° C. and 1 M H2SO4 (aq., 25 mL) was then added. The reaction mixture was then warmed to 20-25° C. and mixed vigorously for 2 hours. The mixture was then poured into a rapidly stirring solution of NaHCO3 (saturated, enough to bring the pH to 7.0). After 5 minutes of stirring, the mixture was extracted twice with TBME and the organic extracts were pooled, dried over Na2SO4, and concentrated to near dryness. The resulting residue was purified by flash column chromatography eluting with 0→40% acetone/hexanes (gradient). Concentration of the fractions containing the title compound gave a crystalline solid (2.23 g, 84% yield).

후처리

  1. customreaction vessel
  2. customAnhydrous, degassed
  3. additionwas then added
  4. temperatureThe resulting solution was then cooled to −78° C.
  5. waitAfter 3-5 minutes
  6. stirringThe solution was then stirred for 8-12 hours at −78° C
  7. temperatureThe reaction mixture was then warmed to 0-5° C.
  8. temperatureThe reaction mixture was then warmed to 20-25° C.
  9. additionmixed vigorously for 2 hours
  10. stirringAfter 5 minutes of stirring
  11. extractionthe mixture was extracted twice with TBME
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated
  14. customThe resulting residue was purified by flash column chromatography
  15. washeluting with 0→40% acetone/hexanes (gradient)
  16. additionConcentration of the fractions containing the title compound

출처 및 근거

ORD 기록
ord-0100347d752e421d8562ff874cd3558d
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759542B2

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