Pyridine → (R)-2-(4-Bromo-2-fluoro-phenylcarbamoyl)-pyrrolidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester

HRID 2217493

반응식

HRID 2217493 반응식
[N:1]1([C:9]([O:11][CH2:12][CH:13]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]3[C:14]2=[CH:15][CH:16]=[CH:17][CH:18]=3)=[O:10])[CH2:8][CH2:7][CH2:6][C@@H:2]1[C:3]([OH:5])=O.S(Cl)(Cl)=O.[Br:30][C:31]1[CH:37]=[CH:36][C:34]([NH2:35])=[C:33]([F:38])[CH:32]=1.N1C=CC=CC=1>ClCCl>[CH:24]1[C:25]2[CH:13]([CH2:12][O:11][C:9]([N:1]3[CH2:8][CH2:7][CH2:6][C@@H:2]3[C:3](=[O:5])[NH:35][C:34]3[CH:36]=[CH:37][C:31]([Br:30])=[CH:32][C:33]=3[F:38])=[O:10])[C:14]3[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:20]=2[CH:21]=[CH:22][CH:23]=1

참가 물질

6

반응물 4

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 1230504-Bromo-2-fluoroanilineHCID 688136(2R)-1-((9H-fluoren-9-ylmethoxy)carbonyl)pyrrolidine-2-carboxylic acid

생성물 1

HCID 68807238(R)-2-(4-Bromo-2-fluoro-phenylcarbamoyl)-pyrrolidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

Fmoc-D-Pro (1.2 g, 3.56 mmol) was suspended in 10 mL dry dichloromethane (DCM), cooled in an ice water bath, and then thionyl chloride (0.78 mL, 10.7 mmol) was added slowly. After addition was complete, the ice water bath was removed and the reaction was stirred at ambient temperature overnight. The solution was concentrated to dryness. The oil was redissolved in 20 mL dry DCM under an Ar atmosphere, and 4-bromo-2-fluoroaniline (0.81 g, 4.3 mmol) was added, followed by dry pyridine (0.87 mL, 10.7 mmol). The mixture was stirred at ambient temperature for 4 hours, then concentrated. The residue was redissolved in 100 mL EtOAc, washed with 1M HCl (3×50 mL), brine (2×50 mL), dried with MgSO4, filtered and concentrated to yield the title product as a sticky oil. (1.8 g, 99%) APCI (AP+): 509.2, 511.2 (M+H)+.

후처리

  1. temperaturecooled in an ice water bath
  2. additionAfter addition
  3. customthe ice water bath was removed
  4. concentrationThe solution was concentrated to dryness
  5. additionwas added
  6. stirringThe mixture was stirred at ambient temperature for 4 hours
  7. concentrationconcentrated
  8. dissolutionThe residue was redissolved in 100 mL EtOAc
  9. washwashed with 1M HCl (3×50 mL), brine (2×50 mL)
  10. dry with materialdried with MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated

출처 및 근거

ORD 기록
ord-b723312899b74317b8a6f17d7fd12bbc
출처 데이터셋
uspto-grants-2008_08
특허 번호
US07407974B2

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