1,1,3,3-Tetramethylguanidine → Methyl-2-(tert-butoxycarbonyl)-3-(7-methyl-2-[{2-[trimethylsilyl]ethoxy}methyl]-2H-indazol-5-yl)acrylate

HRID 2099776Notes

Reaction equation

HRID 2099776 reaction equation
[CH3:1][C:2]1[C:10]2[C:6](=[CH:7][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[N:9]=2)[CH:5]=[C:4]([CH:19]=O)[CH:3]=1.[CH3:21][O:22][C:23](=[O:38])[CH:24]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])P(OC)(OC)=O.CN(C)C(=N)N(C)C>O1CCCC1>[CH3:21][O:22][C:23](=[O:38])[C:24]([C:31]([O:33][C:34]([CH3:36])([CH3:35])[CH3:37])=[O:32])=[CH:19][C:4]1[CH:3]=[C:2]([CH3:1])[C:10]2[C:6](=[CH:7][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:16])([CH3:17])[CH3:18])[N:9]=2)[CH:5]=1

Participants

5

Reactant 3

HCID 664601,1,3,3-TetramethylguanidineHCID 115728627-Methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-5-carbaldehydeHCID 86599651Methyl2-(tert-butoxycarbonyl)-2-(dimethoxyphosphoryl)acetate

Product 1

HCID 69066334Methyl-2-(tert-butoxycarbonyl)-3-(7-methyl-2-[{2-[trimethylsilyl]ethoxy}methyl]-2H-indazol-5-yl)acrylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2-H-indazole-5-carbaldehyde (8.5 g, 29.3 mmol) and methyl-2-(tert-butoxycarbonyl)-2-(dimethoxyphosphoryl)acetate (10 g, 32.2 mmol, 1.1 equiv) in tetrahydrofuran (30 mL) at 0° C. was added tetramethylguanidine (5.9 mL, 49.8 mmol, 1.7 equiv). After 10 min, the ice bath was removed and the reaction stirred at room temperature overnight. The solvent was evaporated and the residue purified by flash chromatography on silica gel to afford 11.2 g (83%). 1H-NMR (CD3OD, 300 MHz) δ −0.05 (s, 9H), 0.84-0.96 (m, 2H), 1.14 (bs, 9H), 2.56 (s, 3H), 3.58-3.70 (m, 2H), 3.82 (s, 3H), 5.73 (s, 2H), 7.41 (s, 1H), 7.45 (s, 1H), 7.84 (s, 1H), 8.41 (s, 1H). Mass spec.: 462.5 (MH)+.

Workup

  1. customthe ice bath was removed
  2. customThe solvent was evaporated
  3. customthe residue purified by flash chromatography on silica gel
  4. customto afford 11.2 g (83%)

Sources & evidence

ORD record
ord-92bfafb5de6f4be9960dfc6af6553213
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

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