Hydrochloric Acid → 1-tert-Butoxycarbonylmethyl-5-chloro-1H-indole-3-carboxylic acid

HRID 1527211Notes

Reaction equation

HRID 1527211 reaction equation
[C:1]([O:5][C:6](=[O:20])[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=2)[C:10]([CH:18]=[O:19])=[CH:9]1)([CH3:4])([CH3:3])[CH3:2].CC(=CC)C.[O-:26]Cl=O.[Na+].P([O-])(O)(O)=O.[Na+].Cl>C1COCC1.C(O)(C)(C)C.O>[C:1]([O:5][C:6]([CH2:7][N:8]1[C:16]2[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=2)[C:10]([C:18]([OH:26])=[O:19])=[CH:9]1)=[O:20])([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 86673814tert-butyl 2-(5-chloro-3-formyl-1H-indol-1-yl)acetate

Product 1

HCID 682837821-tert-Butoxycarbonylmethyl-5-chloro-1H-indole-3-carboxylic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (5-chloro-3-formyl-indol-1-yl)-acetic acid tert-butyl ester (902 mg, 2.92 mmol) in THF (12 mL) and tert-butanol (4.80 mL) were added successively 2-methyl-2-butene (9.27 mL, 88.0 mmol), a solution of NaClO2 (2.64 g, 29.2 mmol) and sodium dihydrogen phosphate (2.80 g, 23.3 mmol) in water (4.80 mL), followed by stirring at RT for 18 h. The reaction mixture was acidified with 0.1N HCl (pH 2 to 3) and extracted with EtOAc (3×). The combined organics were dried (Phase separator) and concentrated in vacuo. The residue was triturated with diethyl ether, the solid was filtered off, washed with diethyl ether and dried in vacuo to afford the title compound as a white solid. MS (LC/MS): 310 [M+H]+; tR (HPLC conditions b): 5.16 min.

Workup

  1. extractionextracted with EtOAc (3×)
  2. customThe combined organics were dried (Phase separator)
  3. concentrationconcentrated in vacuo
  4. customThe residue was triturated with diethyl ether
  5. filtrationthe solid was filtered off
  6. washwashed with diethyl ether
  7. customdried in vacuo

Sources & evidence

ORD record
ord-0b6e830a439a4c1fa9b75c6907c3f0e4
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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