Sodium hydride → (R)-4-[2-nitro-5-(thiophen-3-ylmethoxy)phenoxy]-4-(2-methylphenyl)butyric acid

HRID 322918Notes

Reaction equation

[OH:1][C@@H:2]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH3:14])[CH2:3][CH2:4][C:5]([O-:7])=[O:6].[Na+].[H-].[Na+].F[C:19]1[CH:24]=[C:23]([O:25][CH2:26][C:27]2[CH:31]=[CH:30][S:29][CH:28]=2)[CH:22]=[CH:21][C:20]=1[N+:32]([O-:34])=[O:33]>C1COCC1>[N+:32]([C:20]1[CH:21]=[CH:22][C:23]([O:25][CH2:26][C:27]2[CH:31]=[CH:30][S:29][CH:28]=2)=[CH:24][C:19]=1[O:1][C@@H:2]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH3:14])[CH2:3][CH2:4][C:5]([OH:7])=[O:6])([O-:34])=[O:33]

Participants

Conditions

Temperature: 50 °C

Procedure

A stirred suspension of sodium (R)-4-hydroxy-4-(2-methylphenyl)butanoate (190 mg) in THF (15 mL) is treated with 60% sodium hydride (35 mg) and maintained at 25° for 0.5 hours. The mixture is treated with 2-fluoro-4-(thiophen-3-ylmethoxy)nitrobenzene (220 mg) and maintained at 50° C. for 3 hours. The solution is evaporated. The residue is dissolved in ethyl acetate, washed with water, dried and evaporated. The residue is purified by flash chromatography on silica, eluting with dichloromethane followed by ethyl acetate, followed by recrystallisation from ethyl acetate/pentane to give (R)-4-[2-nitro-5-(thiophen-3-ylmethoxy)phenoxy]-4-(2-methylphenyl)butyric acid (70 mg), a tan coloured solid, mp. 130-131° C. 1H NMR (CHCl3) 2.2-2.9 (4H,m), 2.4 (3H,s), 4.9 (2H, q), 5.5 (1H, q), 6.2 (1H,s), 6.5 (1H,d), 7.0-7.4 (7H,m), 7.9 (1H,d).

Workup

temperaturemaintained at 25° for 0.5 hours
customThe solution is evaporated
dissolutionThe residue is dissolved in ethyl acetate
washwashed with water
customdried
customevaporated
customThe residue is purified by flash chromatography on silica
washeluting with dichloromethane
customfollowed by recrystallisation from ethyl acetate/pentane

Sources & evidence

ORD record: ord-cad6a049ca96463ca497196a04994815
Source dataset: uspto-grants-2001_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06211234B1

Reaction notes

Loading…