Sulfuric acid magnesium salt (1:1) → tert-butyl ((2R)-1-((((9H-fluoren-9-yl)methoxy)carbonyl)(2-(((tert-butyldimethylsilyl)oxy)methyl)-1-cyanoallyl)amino)but-3-en-2-yl)(benzyloxy)carbamate

HRID 627182노트

반응식

HRID 627182 반응식
[Si:1]([O:8][CH2:9][C:10](=[CH2:13])[CH:11]=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[NH2:14][CH2:15][C@H:16]([N:19]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH:17]=[CH2:18].C[Si]([C:39]#[N:40])(C)C.[O-]S([O-])(=O)=O.[Mg+2].C(=O)(O)[O-].[Na+].[C:52](Cl)(=[O:68])[O:53][CH2:54][CH:55]1[C:67]2[CH:66]=[CH:65][CH:64]=[CH:63][C:62]=2[C:61]2[C:56]1=[CH:57][CH:58]=[CH:59][CH:60]=2>C1COCC1>[CH:66]1[C:67]2[CH:55]([CH2:54][O:53][C:52]([N:14]([CH:11]([C:39]#[N:40])[C:10]([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])=[CH2:13])[CH2:15][C@H:16]([N:19]([O:27][CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25])[CH:17]=[CH2:18])=[O:68])[C:56]3[C:61](=[CH:60][CH:59]=[CH:58][CH:57]=3)[C:62]=2[CH:63]=[CH:64][CH:65]=1

참가 물질

8

반응물 6

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 343679-Fluorenylmethyl chloroformate2회HCID 82115Trimethylsilyl cyanide2회HCID 516892Sodium BicarbonateHCID 574134022-({[tert-Butyl(dimethyl)silyl]oxy}methyl)prop-2-enal2회HCID 89863084(R)-tert-butyl 1-aminobut-3-en-2-yl(benzyloxy)carbamate2회

생성물 1

HCID 131735285tert-butyl ((2R)-1-((((9H-fluoren-9-yl)methoxy)carbonyl)(2-(((tert-butyldimethylsilyl)oxy)methyl)-1-cyanoallyl)amino)but-3-en-2-yl)(benzyloxy)carbamate수율 23.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

2-(((tert-butyldimethylsilyl)oxy)methyl)acrylaldehyde (Intermediate 158, 4.76 g, 23.76 mmol) was added to a solution of (R)-tert-butyl (1-aminobut-3-en-2-yl)(benzyloxy)carbamate (Intermediate 156, 5.79 g, 19.80 mmol) in THF (100 mL), followed by addition of trimethylsilyl cyanide (10.62 mL, 79.19 mmol). The mixture was stirred at room temperature overnight. More TMS-CN was added and stirred longer until less starting material seen by LCMS. MgSO4 was added to the reaction mixture and stirred for 1 hr. Sodium bicarbonate (3.33 g, 39.58 mmol) was added, followed by (9H-fluoren-9-yl)methyl carbonochloridate (7.68 g, 29.69 mmol). The resulting mixture was stirred at room temperature overnight. 0.3 eq more FmocCl was added and stirred 5 h more. The mixture was filtered and the filtrate was evaporated. The residue was purified on silica gel column (0-22%, EtOAc/hexane) to afford the title compound (3.32 g, 23.18%) as a pale yellow thick oil.

후처리

  1. stirringstirred longer until less starting material
  2. stirringstirred for 1 hr
  3. stirringThe resulting mixture was stirred at room temperature overnight
  4. stirringstirred 5 h more
  5. filtrationThe mixture was filtered
  6. customthe filtrate was evaporated
  7. customThe residue was purified on silica gel column (0-22%, EtOAc/hexane)

출처 및 근거

ORD 기록
ord-6a54e6992ddc440fa85fd607ce2a328e
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309245B2

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