HCID 15342962, 화합물 → (rac.)-(1R*,5S*)-7-{4-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-phenyl}-9-methyl-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6-dicarboxylic acid 3-tert-butyl ester 6-ethyl ester

HRID 1715449노트

반응식

HRID 1715449 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])=[CH:4][CH:3]=1.[Li]CCCC.[CH2:24]([O:26][C:27]([C:29]1[C@@H:30]2[N:45]([CH3:46])[C@H:34]([CH2:35][C:36]=1OS(C(F)(F)F)(=O)=O)[CH2:33][N:32]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[CH2:31]2)=[O:28])[CH3:25]>C1COCC1.CCOC(C)=O.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:24]([O:26][C:27]([C:29]1[C@@H:30]2[N:45]([CH3:46])[C@H:34]([CH2:35][C:36]=1[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])=[CH:4][CH:3]=1)[CH2:33][N:32]([C:47]([O:49][C:50]([CH3:51])([CH3:53])[CH3:52])=[O:48])[CH2:31]2)=[O:28])[CH3:25]

참가 물질

8

반응물 3

HCID 15342962HCID 15342962, 화합물HCID 44158352(rac.)-(1R*,5S*)-9-Methyl-7-trifluoromethanesulfonyloxy-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6-dicarboxylic acid 3-tert-butyl ester 6-ethyl esterHCID 178418339Butyllithium

생성물 1

HCID 44158058(rac.)-(1R*,5S*)-7-{4-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-phenyl}-9-methyl-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6-dicarboxylic acid 3-tert-butyl ester 6-ethyl ester

시약·촉매·용매 4

HCID 3007855Zincchloride촉매HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

실험 절차

A sol. of [3-(4-bromo-phenyl)-propoxy]-tert-butyl-dimethyl-silane (102.1 g, 310 mmol) in THF (1.50 L) under nitrogen is cooled to −78° C. BuLi (1.5M in hexane, 212 mL, 318 mmol) is added. After 30 min, ZnCl2 (1M in THF, 465 mL, 465 mmol) is added. The mixture is allowed to warm up to rt. (rac.)-(1R*,5S*)-9-Methyl-7-trifluoromethanesulfonyloxy-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6-dicarboxylic acid 3-tert-butyl ester 6-ethyl ester (83.6 g, 155 mmol) in THF (100 mL) and then Pd(PPh3)4 (4.48 g, 3.87 mmol) are added. The mixture is heated to reflux for 30 min, and allowed to cool to rt. The mixture is diluted with EtOAc and washed with aq. 1M NaOH (1×). The org. extracts are dried over MgSO4, filtered, and the solvents are removed under reduced pressure. Purification of the residue by FC (MeOH/CH2Cl2 1:49→1:24→3:47→2:23) yields the title compound (88.6 g, virtually quantitative). LC-MS: tR=0.98 min; ES+: 559.24.

후처리

  1. temperatureThe mixture is heated
  2. temperatureto reflux for 30 min
  3. temperatureto cool to rt
  4. washwashed with aq. 1M NaOH (1×)
  5. dry with materialextracts are dried over MgSO4
  6. filtrationfiltered
  7. customthe solvents are removed under reduced pressure
  8. customPurification of the residue by FC (MeOH/CH2Cl2 1:49→1:24→3:47→2:23)

출처 및 근거

ORD 기록
ord-012ed2ba32de4cd3b46123a9bb22d2a4
출처 데이터셋
uspto-grants-2010_09
특허 번호
US07799805B2

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