Potassium Carbonate → 2-(S)-(4-Hydroxymethyl-1H-indazol-5-ylmethyl)-succinic acid dimethyl ester

HRID 2378853Notes

Reaction equation

HRID 2378853 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH2:7]([O:9][C:10](=[O:33])[C@@H:11]([CH2:18][C:19]1[C:20]([CH2:28][O:29]C(=O)C)=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][N:23]=[CH:22]2)[CH2:12][C:13]([O:15][CH2:16]C)=[O:14])C>CO>[CH3:7][O:9][C:10](=[O:33])[C@@H:11]([CH2:18][C:19]1[C:20]([CH2:28][OH:29])=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][N:23]=[CH:22]2)[CH2:12][C:13]([O:15][CH3:16])=[O:14]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 597320572-(S)-(4-acetoxymethyl-1H-indazol-5-ylmethyl)-succinic acid diethyl ester

Product 1

HCID 597318712-(S)-(4-Hydroxymethyl-1H-indazol-5-ylmethyl)-succinic acid dimethyl esterYield 92%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Potassium carbonate (1.6 g, 11.6 mmol) was added to a solution of 2-(S)-(4-acetoxymethyl-1H-indazol-5-ylmethyl)-succinic acid diethyl ester (2.0 g, 5.5 mmol) in methanol (60 mL). Mixture was stirred at room temperature for 1.5 hours. Reaction was quenched with the addition of 1N hydrochloric acid (30 mL). Methanol was removed from the mixture in vacuo. Remaining aqueous was basified with sodium bicarbonate. Mixture was extracted with ethyl acetate (2×40 mL). Combined organic layers were washed successively with water (30 mL) and brine (30 mL). Organic was dried (magnesium sulfate), filtered then concentrated in vacuo. Desired product was obtained in 92% yield as an amber oil. 1H NMR (300 MHz, CDCl3): δ=8.21 ((s, 1H), 7.34 (d, J=9.2, 1H), 7.17 (d, J=8.8, 1H), 5.02 (dd, J1=12.4, J2=17.9, 1H)3.63 (s, 6H), 3.23 (m, 1H), 2.98 (m, 1H), 2.77 (dd, J1=7.7, J2=16.8, 1H), 2.53 (dd, J1=6.4, J2=16.7, 1H). MS m/e (M+H)−=307.0.

Workup

  1. customReaction
  2. customwas quenched with the addition of 1N hydrochloric acid (30 mL)
  3. customMethanol was removed from the mixture in vacuo
  4. extractionMixture was extracted with ethyl acetate (2×40 mL)
  5. washCombined organic layers were washed successively with water (30 mL) and brine (30 mL)
  6. dry with materialOrganic was dried (magnesium sulfate)
  7. filtrationfiltered
  8. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-82a75077371347df9ed7a88c8477efd5
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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