Potassium Carbonate → (3-Amino-4-chlorophenyl)methanol
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][C:3]=1[N:10]1C(C)=CC(O)=CC1=O.FC1C=C(F)C=CC=1CBr.C([O-])([O-])=O.[K+].[K+].C([O-])(O)=O.[Na+]>CN(C=O)C.C(#N)C.O>[NH2:10][C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][C:2]=1[Cl:1])[CH2:8][OH:9]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 0 °C
Procedure
1-[2-chloro-5-(hydroxymethyl)phenyl]-4-hydroxy-6-methylpyridin-2(1H)-one (from step 2) (3.5 g, 13.2 mmol) was taken up in DMF (10 ml) and cooled to 0° C. 2,4-Difluorobenzyl bromide (1.7 ml, 13.2 mmol) and K2CO3 (1.8 g, 13.2 mmol) were added and the reaction stirred for 6 hours. The reaction was worked up by adding saturated NaHCO3 (aq.) and extracting with ethyl acetate. The ethyl acetate extraction was washed with water, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined and dried over Na2SO4, filtered, and the solvent removed in vacuo. The product was obtained in 83% crude yield and carried through to the next step as a brown oil. LC/MS, tr=2.48 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 392 (M+H). ES-HRMS m/z 392.0853 (M+H calcd for C20H17ClF2NO3 requires 392.0860).
Workup
- extractionextracting with ethyl acetate
- extractionThe ethyl acetate extraction
- washwas washed with water
- extractionthe aqueous layer was extracted with ethyl acetate
- dry with materialdried over Na2SO4
- filtrationfiltered
- customthe solvent removed in vacuo
- customThe product was obtained in 83% crude yield
Sources & evidence
- ORD record
- ord-c1002abed9c844b593904e178ad7cdba
- Source dataset
- uspto-grants-2006_06
- Patent number
- US07067540B2
Reaction notes
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