Acetic Acid → (R)-3-(4-(acetoxymethyl)-7-chloro-1H-indazol-5-yl)-1-methoxy-1-oxopropan-2-yl benzoate

HRID 2378906Notes

Reaction equation

HRID 2378906 reaction equation
[C:1]([O:9][C@H:10]([CH2:15][C:16]1[CH:21]=[C:20]([Cl:22])[C:19]([NH2:23])=[C:18]([CH3:24])[C:17]=1[CH2:25][O:26][C:27](=[O:29])[CH3:28])[C:11]([O:13][CH3:14])=[O:12])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.C(O)(=O)C.[N:41](OCCC(C)C)=O.C([O-])(=O)C.[K+]>>[C:1]([O:9][C@H:10]([CH2:15][C:16]1[C:17]([CH2:25][O:26][C:27](=[O:29])[CH3:28])=[C:18]2[C:19](=[C:20]([Cl:22])[CH:21]=1)[NH:23][N:41]=[CH:24]2)[C:11]([O:13][CH3:14])=[O:12])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 1140TolueneHCID 8053Isoamyl NitriteHCID 517044Potassium AcetateHCID 59732080(R)-3-(2-(acetoxymethyl)-4-amino-5-chloro-3-methylphenyl)-1-methoxy-1-oxopropan-2-yl benzoate

Product 1

HCID 59732064(R)-3-(4-(acetoxymethyl)-7-chloro-1H-indazol-5-yl)-1-methoxy-1-oxopropan-2-yl benzoateYield 88%

Procedure

(R)-3-(2-(acetoxymethyl)-4-amino-5-chloro-3-methylphenyl)-1-methoxy-1-oxopropan-2-yl benzoate (16.33 g, 38.9 mmol) in toluene (100.0 ml, 939 mmol) was added acetic acid (5.0 ml, 87 mmol) followed by isoamyl nitrite (5.76 ml, 42.8 mmol) at 0° C. After 15 min, potassium acetate (7.64 g, 78 mmol) was added and the reaction mixture was stirred for 12 h. The solvent was removed and the crude product was dissolved in dichloromethane (250 mL) and washed with aqueous NaHCO3. The solvent was dried (Na2SO4), evaporated and the crude product was purified by flash chromatography using 40% EtOAc in hexane to give (R)-3-(4-(acetoxymethyl)-7-chloro-1H-indazol-5-yl)-1-methoxy-1-oxopropan-2-yl benzoate in 88% yield. MS (ESI) 453 (M+Na); Rf=2.46.

Workup

  1. customThe solvent was removed
  2. dissolutionthe crude product was dissolved in dichloromethane (250 mL)
  3. washwashed with aqueous NaHCO3
  4. dry with materialThe solvent was dried (Na2SO4)
  5. customevaporated
  6. customthe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-ffe28a0ca012433bb81141caf71925f1
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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