Isoamyl Nitrite → (S)-Diethyl 2-((4-(acetoxymethyl)-7-chloro-1H-indazol-5-yl)methyl)succinate

HRID 1985456Notes

Reaction equation

HRID 1985456 reaction equation
[N:1](OCCC(C)C)=O.[CH2:9]([O:11][C:12](=[O:35])[C@@H:13]([CH2:20][C:21]1[CH:26]=[C:25]([Cl:27])[C:24]([NH2:28])=[C:23]([CH3:29])[C:22]=1[CH2:30][O:31][C:32](=[O:34])[CH3:33])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH3:10].C([O-])(=O)C.[K+]>C(O)(=O)C.C1(C)C=CC=CC=1>[CH2:9]([O:11][C:12](=[O:35])[C@@H:13]([CH2:20][C:21]1[C:22]([CH2:30][O:31][C:32](=[O:34])[CH3:33])=[C:23]2[C:24](=[C:25]([Cl:27])[CH:26]=1)[NH:28][N:1]=[CH:29]2)[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH3:10]

Participants

6

Reactant 3

HCID 8053Isoamyl NitriteHCID 517044Potassium AcetateHCID 597319572-(S)-(2-Acetoxymethyl-4-amino-5-chloro-3-methyl-benzyl)-succinic acid diethyl ester

Product 1

HCID 59731976(S)-Diethyl 2-((4-(acetoxymethyl)-7-chloro-1H-indazol-5-yl)methyl)succinateYield 80%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

Isoamyl nitrite (700 μL, 5.2 mmol), was added dropwise to an ice cold solution of 2-(S)-(2-Acetoxymethyl-4-amino-5-chloro-3-methyl-benzyl)-succinic acid diethyl ester (1.91 g, 4.8 mmol) in 5% acetic acid in toluene (81.2 mL). Mixture stirred at 0° C. for 45 minutes. Potassium acetate (1.50 g, 15.3 mmol) was added to the mixture. Reaction was stirred at room temperature for 14 hours. Mixture was quenched with water. Mixture was extracted with ethyl acetate (30 mL). Mixture was washed 2× saturated aqueous sodium bicarbonate. Organic was dried (magnesium sulfate) filtered and concentrated. Silica gel chromatography (ethyl acetate-hexanes) afforded the desired product in 80% yield as an amber oil. 1H NMR (300 MHz, CDCl3): δ=8.23 (s, 1H), 7.26 (s, 1H), 5.45 (s, 2H), 4.09 (q, J=7.0, 4H), 3.20 (dd, J1=7.32, J2=13.2, 1H), 3.10 (m, 1H), 2.97 (dd, J1=7.0, J2=13.3, 1H), 2.73 (dd, J1=8.4, J2=16.8, 1H), 2.44 (dd, J1=5.5, J2=16.8, 1H), 2.08 (s, 3H), 1.18 (m, 6H). MS m/e (M+H)+=411.0.

Workup

  1. customReaction
  2. stirringwas stirred at room temperature for 14 hours
  3. customMixture was quenched with water
  4. extractionMixture was extracted with ethyl acetate (30 mL)
  5. washMixture was washed 2× saturated aqueous sodium bicarbonate
  6. dry with materialOrganic was dried (magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-65680b8863e745de9fab07ae9d80aed2
Source dataset
uspto-grants-2009_06
Patent number
US07544680B2

Reaction notes

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