Sodium Carbonate → 3-Chloro-4-(3,3,3-trifluoro-2-hydroxy-1-methyl-2-quinolin-3-yl-propyl)-phenol

HRID 1097939Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6]([O:8]C)[CH:5]=[CH:4][C:3]=1[CH:10]([CH3:27])[C:11]([C:17]1[CH:18]=[N:19][C:20]2[C:25]([CH:26]=1)=[CH:24][CH:23]=[CH:22][CH:21]=2)([OH:16])[C:12]([F:15])([F:14])[F:13].C([O-])([O-])=O.[Na+].[Na+]>Br>[Cl:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[CH:10]([CH3:27])[C:11]([OH:16])([C:17]1[CH:18]=[N:19][C:20]2[C:25]([CH:26]=1)=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:12]([F:14])([F:13])[F:15]

Participants

Conditions

Temperature: 120 °C

Procedure

3-(2-Chloro-4-methoxy-phenyl)-1,1,1-trifluoro-2-quinolin-3-yl-butan-2-ol (Example 178, 2.60 g) was suspended in aqueous HBr (48%, 52 ml). The mixture was stirred for 16 h at 80° C., for 20 h at 105° C., for 7 h at 110° C. and for 6 h at 120° C. The reaction mixture was poured into ice water/EtOAc, neutralized with aqueous sat. Na2CO3 solution and extracted with EtOAc. The organic phase was washed with water and dried (MgSO4). The product was purified by chromatography (SiO2, cyclohexane=>cyclohexane/EtOAc 1:1=>EtOAc/MeOH 9:1=>1:1) and subsequently precipitated from hot EtOAc to give the title compound (1.83 g) as an off-white solid. MS (m/e)=382.1 [M+H+].

Workup

extractionextracted with EtOAc
washThe organic phase was washed with water
dry with materialdried (MgSO4)
customThe product was purified by chromatography (SiO2, cyclohexane=>cyclohexane/EtOAc 1:1=>EtOAc/MeOH 9:1=>1:1)
customsubsequently precipitated from hot EtOAc

Sources & evidence

ORD record: ord-828617d8ddaa4febb51301ef97e98ca0
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08143280B2

Reaction notes

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