3-Chlorophenol → 4-Bromo-3-chlorophenol

HRID 840424Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.FC1C=C(C(CCN2CCC(C3C=CC=CC=3[S@](C)=O)CC2)CN(C)C(C2C3C(=CC=CC=3)C=C([N+]([O-])=O)C=2)=O)C=CC=1F.[Br:66]Br>>[Br:66][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=1[OH:8].[Br:66][C:7]1[CH:6]=[CH:5][C:4]([OH:8])=[CH:3][C:2]=1[Cl:1]

Participants

Reactant 3

HCID 79333-Chlorophenol2×

HCID 24408Bromine

HCID 70158743HCID 70158743, compound

Product 2

HCID 70181824-Bromo-3-chlorophenol

HCID 132842722-Bromo-5-chlorophenol

Procedure

The requisite 4-(4-chloro-2-(R,S)-methylsulfinylphenyl)piperidine was prepared according to the procedures described in Example 2 except 3-chlorophenol was used in place of 3-methoxyphenol. The oxidation of the thiomethyl adduct was carried out according to the procedure described in Example 16, sub-part (e). 3-Chlorophenol (24.28 g) was reacted with bromine (29.78 g) to give 6.15 g of 2-bromo-5-chlorophenol (minor isomer) and 24.60 g 4-bromo-3-chlorophenol (major isomer) after purification by column chromatography (10:1 hexane:EtOAc); minor isomer-1H NMR (CDCl3) δ 7.37 (d, 1H), 7.04 (d, 1H), 6.82 (dd, 1H), 5.55 (s, 1H). Major isomer: 1H NMR (CDCl3) δ 7.36 (d, 1H), 6.91 (d, 1H), 6.57 (dd, 1H), 5.75 (s, 1H). Analytical data for all other intermediates follows. 2-Bromo-5-chloro-(N,N-dimethylthiocarbamoyl)phenol; 1H NMR (CDCl3) δ 7.52 (d, 1H), 7.18 (d, 1H), 7.13 (dd, 1H), 3.47 (s, 3H), 3.39 (s, 3H); MS m/z 296 (M+). 4-Chloro-2-N,N-dimethylthiocarbamoyl)bromobenzene; 1H NMR (CDCl3) δ 7.68-7.55 (m, 2H), 7.23 (dd, 1H), 3.12 (s, 3H), 3.05 (s, 3H); MS m/z 296 (M+). 4-Chloro-2-(thiomethyl)bromobenzene; 1H NMR (CDCl3) δ 7.43 (d, 1H), 7.06 (d, 1H), 6.97 (dd, 1H), 2.48 (s, 3H). 1-Benzyloxycarbonyl-4-hydroxy-4-(4-chloro-2-methylthiophenyl)piperidine; 1H NMR (CDCl3) δ 7.43-7.30 (m, 6H), 7.26 (d, 1H), 7.15 (dd, 1H) 5.15 (s, 2H), 4.25-4.00 (m, 2H), 3.84 (s, 1H), 3.50-3.25 (m, 2H), 2.52 (s, 3H), 2.15-1.90 (m, 4H); MS m/z 414 (M+Na). 1-Benzyloxycarbonyl-4-(4-chloro-2-methylthiophenyl)piperidine; 1H NMR (CDCl3) δ 7.43-7.30 (m, 5H), 7.18-7.10 (m, 3H), 5.16 (s, 2H), 4.42-4.20 (m, 2H), 3.07 (tt, 1H), 3.00-2.80 (m, 2H), 2.47 (s, 3H), 1.91-1.45 (m, 4H); MS m/z 398 (M+Na). 1-Benzyloxycarbonyl-4-(4-chloro-2-(R,S)-methylsulfinylphenyl)piperidine; 1H NMR (CDCl3) δ 7.98 (d, 1H), 7.42 (dd, 1H), 7.41-7.30 (m, 5H), 7.21 (d, 1H), 5.16 (s, 2H), 4.43-4.21 (m, 2H), 2.96-2.78 (m, 3H), 2.71 (s, 3H), 1.92-1.51 (m, 4H). 4-(4-Chloro-2-(R,S)-methylsulfinylphenyl)piperidine; 1H NMR (CDCl3) δ 7.97 (d, 1H), 7.43 (dd, 1H), 7.28 (d, 1H), 3.30-3.10 (m, 2H), 2.71 (s, 3H), 2.83-2.61 (m, 3H), 1.92-1.51 (m, 5H); MS m/z 258 (M+H).

Sources & evidence

ORD record: ord-9d334fb977004bf9805a40c3672af5a7
Source dataset: uspto-grants-2002_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06365602B1

Reaction notes

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