Hydrochloric Acid → Methyl 4-chloro-3,5-diisopropoxybenzoate

HRID 62750Notes

Reaction equation

N(OC(C)(C)C)=O.N[C:9]1[C:18]([O:19][CH:20]([CH3:22])[CH3:21])=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10]=1[O:23][CH:24]([CH3:26])[CH3:25].[ClH:27]>CC#N.[Cu]Cl>[Cl:27][C:9]1[C:18]([O:19][CH:20]([CH3:22])[CH3:21])=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10]=1[O:23][CH:24]([CH3:26])[CH3:25]

Participants

Conditions

Temperature: 65 °C

Procedure

A suspension of copper (I) chloride (129 mg, 1.31 mmol) and tert-butyl nitrite (155 μL, 1.31 mmol) in anhydrous MeCN (2 mL) was stirred at 65° C. A solution of methyl 4-amino-3,5-diisopropoxybenzoate (4) (233 mg, 0.872 mmol) in anhydrous MeCN (1 mL) was added dropwise. Once the addition was complete the mixture was allowed to cool to RT and poured on to 20% HCl (5 mL). The mixture was partitioned between DCM (10 mL) and aq. ammonia (35%, 5 mL), the phases were separated and the organic solution was further washed with ammonia solution (17.5%, 10 mL), and brine (2×20 mL). The solvent was removed in vacuo and the residue was purified by silica gel chromatography (40 g, 0-100% EtOAc in isohexane) to afford methyl 4-chloro-3,5-diisopropoxybenzoate (93 mg, 36% yield) as a colourless oil: m/z 287 [M+H]+ (ES+).

Workup

additionOnce the addition
temperatureto cool to RT
customThe mixture was partitioned between DCM (10 mL) and aq. ammonia (35%, 5 mL)
customthe phases were separated
washthe organic solution was further washed with ammonia solution (17.5%, 10 mL), and brine (2×20 mL)
customThe solvent was removed in vacuo
customthe residue was purified by silica gel chromatography (40 g, 0-100% EtOAc in isohexane)

Sources & evidence

ORD record: ord-ee66a503bb9b42dabd090455d8b78dc4
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09447028B2

Reaction notes

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