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 627182Notes

Reaction equation

HRID 627182 reaction equation
[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

Participants

8

Reactant 6

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 343679-Fluorenylmethyl chloroformate2×HCID 82115Trimethylsilyl cyanide2×HCID 516892Sodium BicarbonateHCID 574134022-({[tert-Butyl(dimethyl)silyl]oxy}methyl)prop-2-enal2×HCID 89863084(R)-tert-butyl 1-aminobut-3-en-2-yl(benzyloxy)carbamate2×

Product 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)carbamateYield 23.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-6a54e6992ddc440fa85fd607ce2a328e
Source dataset
uspto-grants-2016_04
Patent number
US09309245B2

Reaction notes

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