Tetrahydrofuran → (S)-tert-butyl 3-(amino(3-chloro-4-fluorophenyl)methyl)pyrrolidine-1-carboxylate

HRID 715065노트

반응식

HRID 715065 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([N:22]2C(=O)C3C(=CC=CC=3)C2=O)[C@H:10]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11]2)[CH:5]=[CH:6][C:7]=1[F:8].C1COCC1.O.NN>CO>[NH2:22][CH:9]([C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=1)[C@H:10]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11]1

참가 물질

5

반응물 3

HCID 8028TetrahydrofuranHCID 24654Hydrazine hydrate (1:1)HCID 117965489(3S)-tert-butyl 3-((3-chloro-4-fluorophenyl)(1,3-dioxoisoindolin-2-yl)methyl)pyrrolidine-1-carboxylate

생성물 1

HCID 71246607(S)-tert-butyl 3-(amino(3-chloro-4-fluorophenyl)methyl)pyrrolidine-1-carboxylate수율 72.3%

시약·촉매·용매 1

HCID 887Methanol용매

반응 조건

온도
60 °C

실험 절차

A solution of 71a/71b (212.3 mg, 0.4626 mmol) in 1:1 THF:MeOH (2.3 mL, 0.2 M) was treated with hydrazine monohydrate (224.4 μL, 4.626 mmol) and heated to 60° C. overnight. The reaction was cooled to RT, and the solids were filtered off. The filtrate was concentrated to dryness and taken up in EtOAc (30 mL). The EtOAc solution was washed with saturated NaHCO3 (2×30 mL) and brine (1×30 mL). The organics were isolated, dried (Na2SO4), filtered and concentrated. The crude product was purified by SiO2 chromatography eluting with a 1-25% gradient of MeOH/3% NH4OH in DCM to afford 110 mg (72%) of 73a/73b as a clear oil containing approximately a 1:1 mixture of diastereomers.

후처리

  1. temperatureThe reaction was cooled to RT
  2. filtrationthe solids were filtered off
  3. concentrationThe filtrate was concentrated to dryness
  4. washThe EtOAc solution was washed with saturated NaHCO3 (2×30 mL) and brine (1×30 mL)
  5. customThe organics were isolated
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by SiO2 chromatography
  10. washeluting with a 1-25% gradient of MeOH/3% NH4OH in DCM

출처 및 근거

ORD 기록
ord-2b898ce841f1480b99037f9f151d004a
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09187462B2

반응 노트

불러오는 중…