Cesium carbonate → (1R,3S)-methyl 1-amino-3-(4-(7-methoxyhept-1-ynyl)phenyl)cyclopentanecarboxylate

HRID 1511843노트

반응식

HRID 1511843 반응식
Cl.[NH2:2][C@:3]1([C:15]([O:17][CH3:18])=[O:16])[CH2:7][CH2:6][C@H:5]([C:8]2[CH:13]=[CH:12][C:11](Br)=[CH:10][CH:9]=2)[CH2:4]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:59][O:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][C:66]#[CH:67]>C(#N)C.C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl>[NH2:2][C@:3]1([C:15]([O:17][CH3:18])=[O:16])[CH2:7][CH2:6][C@H:5]([C:8]2[CH:13]=[CH:12][C:11]([C:67]#[C:66][CH2:65][CH2:64][CH2:63][CH2:62][CH2:61][O:60][CH3:59])=[CH:10][CH:9]=2)[CH2:4]1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 44191914Methyl (1R,3S)-1-amino-3-(4-bromophenyl)cyclopentane-1-carboxylate hclHCID 575547897-Methoxyhept-1-yne

생성물 1

HCID 68936341(1R,3S)-methyl 1-amino-3-(4-(7-methoxyhept-1-ynyl)phenyl)cyclopentanecarboxylate수율 97.4%

시약·촉매·용매 2

HCID 498840Bis(benzonitrile)palladium chloride촉매HCID 6342Acetonitrile용매

반응 조건

온도
90 °C

실험 절차

To a 50 mL round bottomed flask equipped with a reflux condenser was charged successively (1R,3S)-methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate hydrochloride salt (0.500 g, 1.494 mmol), trans-bis(benzonitrile)dichloropalladium(II) (0.029 g, 0.075 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (0.107 g, 0.224 mmol), and cesium carbonate (1.947 g, 5.98 mmol). The flask was evacuated and back-filled with nitrogen for three cycles. Then 7-methoxyhept-1-yne (1.16 g, 9.19 mmol) as a solution in acetonitrile (7.0 ml) was added via syringe. The reaction mixture was heated to about 90° C. After about 4 hours the reaction mixture was cooled to ambient temperature and partitioned into water (50 mL) and ethyl acetate (50 mL). The organic phase was separated, washed with saturated sodium bicarbonate solution (50 mL), brine (50 mL), then dried (MgSO4) and concentrated to yield 1.98 g of crude yellow oil. The crude material was purified via Analogix flash chromatography system using RediSep RS 12 g column, with a gradient of 0-5% methanol in ethyl acetate over 25 min. at 15 mL/min. Fractions containing product were combined and concentrated to yield 0.5 g of greenish yellow oil of (1R,3S)-methyl 1-amino-3-(4-(7-methoxyhept-1-ynyl)phenyl)cyclopentanecarboxylate which was used in the next step without further purification.

후처리

  1. customTo a 50 mL round bottomed flask equipped with a reflux condenser
  2. customThe flask was evacuated
  3. additionback-filled with nitrogen for three cycles
  4. temperatureAfter about 4 hours the reaction mixture was cooled to ambient temperature
  5. custompartitioned into water (50 mL) and ethyl acetate (50 mL)
  6. customThe organic phase was separated
  7. washwashed with saturated sodium bicarbonate solution (50 mL), brine (50 mL)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customto yield 1.98 g of crude yellow oil
  11. customThe crude material was purified via Analogix flash chromatography system
  12. additionFractions containing product
  13. concentrationconcentrated

출처 및 근거

ORD 기록
ord-5cf1e57ba16441059002620f96534e61
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08217027B2

반응 노트

불러오는 중…