Phosphorus trichloride → 3-hydroxy-N-(3-isopropylphenyl)-4-methylbenzamide

HRID 883026Notes

Reaction equation

[OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([OH:7])=O.[CH:12]([C:15]1[CH:16]=[C:17]([NH2:21])[CH:18]=[CH:19][CH:20]=1)([CH3:14])[CH3:13].P(Cl)(Cl)Cl>CN(C1C=CN=CC=1)C.C1(C)C=CC=CC=1.[Cl-].[Na+].O.C(OCC)(=O)C>[OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([NH:21][C:17]1[CH:18]=[CH:19][CH:20]=[C:15]([CH:12]([CH3:14])[CH3:13])[CH:16]=1)=[O:7]

Participants

Conditions

Temperature: 135 °C

Procedure

3-Hydroxy-4-methylbenzoic acid (1.07 g, 7.00 mmol), 3-isopropylbenzenamine (0.90 mL, 6.4 mmol), and DMAP (0.27 g, 2.2 mmol) were suspended in 25 mL dry toluene in a 2-neck flask with an attached Dean-Stark trap under N2. The mixture was stirred in a 135° C. oil bath and brought to a boil before PCl3 (0.28 mL, 3.2 mmol) was added dropwise by glass/Teflon syringe over 15 minutes. Heating was continued an additional 25 minutes. After cooling, the mixture was diluted with brine and ethyl acetate, and acidified with 1 NHC1. After extraction, the organic layer was dried over anhydrous Na2SO4, concentrated, and purified by flash chromatography (20-50% EtOAc/hexanes) to yield 3-hydroxy-N-(3-isopropylphenyl)-4-methylbenzamide as a white solid after concentration. MS m/z=268 [M−1]−. Calc'd for C17H19NO2: 269.35.

Workup

temperatureHeating
temperatureAfter cooling
extractionAfter extraction
dry with materialthe organic layer was dried over anhydrous Na2SO4
concentrationconcentrated
custompurified by flash chromatography (20-50% EtOAc/hexanes)

Sources & evidence

ORD record: ord-90b15b57782a4e64bab51e6735bda200
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08236823B2

Reaction notes

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