Sodium Hydroxide → Methyl 2-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)acetate

HRID 913917Notes

Reaction equation

HRID 913917 reaction equation
[OH-].[Na+].[CH3:3]N(N=O)C(N[N+]([O-])=O)=N.[Cl:13][C:14]1[CH:22]=[C:21]([CH2:23][C:24]([OH:26])=[O:25])[C:20]2[C:16](=[CH:17][N:18]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[N:19]=2)[CH:15]=1>C(OCC)C>[Cl:13][C:14]1[CH:22]=[C:21]([CH2:23][C:24]([O:26][CH3:3])=[O:25])[C:20]2[C:16](=[CH:17][N:18]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:33])([CH3:32])[CH3:34])[N:19]=2)[CH:15]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 575462532-(5-Chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)acetic acidHCID 135436526N-Methyl-N'-nitro-N-nitrosoguanidine

Product 1

HCID 57545943Methyl 2-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)acetate

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a heterogeneous mixture of sodium hydroxide (4M in water, 25 mL) and diethyl ether (75 mL) at 0° C. was added N-methyl-N′-nitro-N-nitrosoguanidine (2.24 g, 15.3 mmol) with swirling (no stirbar). After addition was complete, the mixture was allowed to stand at 0° C. for 15 min with occasional swirling. The ethereal was transferred in portions to a suspension of 2-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)acetic acid (2.6 g, 7.63 mmol) in diethyl ether (50 mL) until the yellow color persisted and all of the starting material had gone into solution. The reaction was allowed to rest at room temperature for 5 min before bubbling nitrogen through the solution to remove most of the unreacted diazomethane. Column chromatography (25% ethyl acetate/n-hexane) gave 2.28 g (84%) as a colorless oil. 1H-NMR (CDCl3, 500 MHz) δ 8.02 (s, 1H), 7.56 (d, J=1.5 Hz, 1H), 7.14 (d, J=0.9 Hz, 1H), 5.67 (s, 2H), 4.01 (s, 2H), 3.70 (s, 3H), 3.61 (t, J=8.2 Hz, 2H), 0.92 (t, J=8.3 Hz, 2H), −0.04 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 171.3, 146.9, 127.7, 127.5, 126.0, 122.61, 122.57, 118.3, 82.0, 67.7, 52.1, 36.1, 17.9, −1.4.

Workup

  1. additionAfter addition
  2. waitto rest at room temperature for 5 min
  3. custombefore bubbling nitrogen through the solution
  4. customto remove most of the unreacted diazomethane
  5. customColumn chromatography (25% ethyl acetate/n-hexane) gave 2.28 g (84%) as a colorless oil

Sources & evidence

ORD record
ord-753e34cde1564f6f842a60c512173bdf
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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