(R)-2-chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazole → HCID 68454656, compound

HRID 2354026Notes

Reaction equation

HRID 2354026 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([O:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[Cl:26][C:27]1[N:28]([CH2:35][C@@:36]2([CH3:39])[O:38][CH2:37]2)[CH:29]=[C:30]([N+:32]([O-:34])=[O:33])[N:31]=1>>[Cl:26][C:27]1[N:28]([CH2:35][C@:36]([OH:38])([CH3:37])[CH2:39][O:1][C:2]2[CH:3]=[CH:4][C:5]([N:8]3[CH2:9][CH2:10][CH:11]([O:14][C:15]4[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:23])[F:24])=[CH:17][CH:16]=4)[CH2:12][CH2:13]3)=[CH:6][CH:7]=2)[CH:29]=[C:30]([N+:32]([O-:34])=[O:33])[N:31]=1

Participants

3

Reactant 2

HCID 10443353(R)-2-chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazoleHCID 11653258SS-3227

Product 1

HCID 68454656HCID 68454656, compound

Conditions

Temperature
100 °C

Procedure

1-(4-hydroxyphenyl)-4-(4-trifluoromethoxyphenoxy)piperidine (2034 g) and 2-chloro-1-[(2R)-2-methyl-2,3-epoxypropyl]-4-nitroimidazole (1388 g) were heated with stirring for 8 hours at about 100° C. and crude 1-{4-[(2R)-3-(2-chloro-4-nitroimidazole-1-yl)-2-hydroxy-2-methylpropoxy]phenyl}-4-(4-trifluoromethoxyphenoxy)piperidine was obtained. At the point where this was cooled to 88° C., dimethylformamide (2.5 L) was added and dissolved therein. After leaving the mixture at room temperature for 13 hours, dimethylformamide (15.8 L) was further added and the mixture was cooled to −9° C. Sodium tert-butoxide (715 g) was gradually added thereto at not more than 0° C. over 3.5 hours. After stirring for further 15 minutes, the reaction mixture was poured into a mixture of water (41.2 L) and ethyl acetate (2.1 L) at room temperature. After stirring for an hour at 30° C., the precipitate was filtrated. Crystals were washed with water (9.2 L) and then with ethyl acetate (8.2 L) under reflux. Upon cooling to 5° C., the precipitate was filtrated. The precipitate washed with ethyl acetate (2.2 L), and dried by air blasting at 60° C. for 18 hours to obtain (2R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethoxyphenoxy)piperidine-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole (1548 g; yield 50%).

Sources & evidence

ORD record
ord-bb738ffaa2544ac5a127b432c2ac6ee7
Source dataset
uspto-grants-2010_07
Patent number
US07750156B2

Reaction notes

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