Hydrochloric Acid → N-hydroxy-5-[(2-phenyl-4-thiazolyl)methoxy]-1-(phenylmethyl)-N,2-dimethyl-1H-indole-3-acetamide

HRID 37718

Reaction equation

HRID 37718 reaction equation
[C:1]1([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH2:18][C:19]4[N:20]=[C:21]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[S:22][CH:23]=4)=[CH:14][CH:15]=3)[C:10]([CH2:30][C:31](O)=[O:32])=[C:9]2[CH3:34])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.Cl.[CH3:42][NH:43][OH:44].Cl>C(Cl)Cl.C(N(CC)CC)C.O.O1CCCC1.CC(N(C)C)=O>[OH:44][N:43]([CH3:42])[C:31](=[O:32])[CH2:30][C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[C:13]([O:17][CH2:18][C:19]3[N:20]=[C:21]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)[S:22][CH:23]=3)[CH:12]=2)[N:8]([CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:9]=1[CH3:34]

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 65578Oxalyl chlorideHCID 77906N-methylhydroxylamine hydrochlorideHCID 152880281-[(Phenyl)methyl]-2-methyl-5-[(2-phenyl-4-thiazolyl)methoxy]-1H-indole-3-acetic acid

Product 1

HCID 15288043N-hydroxy-5-[(2-phenyl-4-thiazolyl)methoxy]-1-(phenylmethyl)-N,2-dimethyl-1H-indole-3-acetamideYield 57%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
5 °C

Procedure

A mixture of the compound of Example 40 (1.0 g, 2.13 mmol), methylene chloride (50 mL) and dimethylacetamide (0.15 mL) is cooled to 5° C. and with stirring, a solution of oxalyl chloride (0.45 mL, 5.3 mmol) in methylene chloride (10 mL) is added slowly. After stirring at room temperature for 30 minutes, the reaction mixture is poured into a solution containing tetrahydrofuran (11 mL), water (1.1 mL), triethylamine (1.8 mL) and N-methylhydroxylamine hydrochloride (0.7 g, 8.5 mmol). After stirring at room temperature for 1 hour, the reaction mixture is diluted with methylene chloride (150 mL), poured into 2N HCl (150 mL) and the layers are separated. The aqueous layer is washed again with methylene chloride (100 mL). The combined methylene chloride extract is washed with water (100 mL) and brine (100 mL), dried over MgSO4 and concentrated under reduced pressure to give 1.0 g of a crude solid. The solid is recrystallized from ether/methylene chloride to give 0.6 g of white crystalline product in 57 % yield, m.p. 171°-173° C.

Workup

  1. stirringAfter stirring at room temperature for 30 minutes
  2. additionthe reaction mixture is poured into a solution
  3. stirringAfter stirring at room temperature for 1 hour
  4. customthe layers are separated
  5. washThe aqueous layer is washed again with methylene chloride (100 mL)
  6. extractionThe combined methylene chloride extract
  7. washis washed with water (100 mL) and brine (100 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customto give 1.0 g of a crude solid
  11. customThe solid is recrystallized from ether/methylene chloride

Sources & evidence

ORD record
ord-8f69cf4c756f4fb8bd6d78b4fee31505
Source dataset
uspto-grants-1995_05
Patent number
US05420289

Linked notes

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