Thionyl Chloride → (R)-3-Bromo-2-hydroxy-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide

HRID 890380Notes

Reaction equation

HRID 890380 reaction equation
S(Cl)(Cl)=O.[Br:5][CH2:6][C@@:7]([OH:12])([CH3:11])[C:8](O)=[O:9].[N+:13]([C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][C:17]=1[C:23]([F:26])([F:25])[F:24])([O-:15])=[O:14]>CC(N(C)C)=O>[N+:13]([C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:8](=[O:9])[C@:7]([OH:12])([CH3:11])[CH2:6][Br:5])=[CH:18][C:17]=1[C:23]([F:24])([F:25])[F:26])([O-:15])=[O:14]

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 949554-Nitro-3-(trifluoromethyl)anilineHCID 10582468(2R)-3-bromo-2-hydroxy-2-methylpropanoic acid

Product 1

HCID 5287785(R)-3-Bromo-2-hydroxy-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamideYield 80.8%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

Thionyl chloride (8.6 g, 72 mmol) was added dropwise under argon to a solution of bromoacid R-131 (11.0 g, 60 mmol) in 70 mL of DMA at −5 to −10° C. The resulting mixture was stirred for 2 h under the same conditions. A solution of 4-nitro-3-trifluoromethyl-aniline (12.4 g, 60 mmol) in 80 mL of DMA was added dropwise to the above solution, and the resulting mixture was stirred overnight at room temperature. The solvent was removed on Rotavapor using high vacuum oil pump; the residue was diluted with saturated NaHCO3 solution, and extracted with ethyl ether (100 mL×3). Combined extracts were dried over anhydrous Na2SO4, filtered through Celite, and purified by flash chromatography on silica gel, using methylene chloride as eluent to afford 18.0 g (80%) of the desired compound: mp 98100° C. (Rf=0.2, silica gel, CH2Cl2); 1H NMR (300 MHz, DMSO-d6) δ 10.54 (s, 1H, NH), 8.54 (d, J=2.1 Hz, 1H, ArH), 8.34 (dd, J=9.0 Hz, J=2.1 Hz, 1H, ArH), 8.18 (d, J=9.0 Hz, 1H, ArH), 6.37 (s, 1H, OH), 3.82 (d, J=10.4 Hz, 1H, CHHa), 3.58 (d, J=10.4 Hz, 1H, CHHb), 1.48 (s, 3H, Me); 13C NMR (75 MHz, DMSO-d6) δ 173.6 (C═O), 143.0, 127.2, 123.2, 122.6 (q, J=33.0 Hz), 122.0 (q, J=271.5 Hz), 118.3 (q, J=6.0 Hz), 74.4, 41.4, 24.9; IR (KBr) 3344 (OH), 1680 (C═O), 1599, 1548 (C═C, Ar), 1427, 1363, 1161 cm−1; MS (ESI): m/z 370.8 (M)+; Anal. Calcd. for C11H10BrN2O4: C 35.60, H 2.72, N 7.55. Found: C 35.68, H 2.72, N 7.49.

Workup

  1. stirringthe resulting mixture was stirred overnight at room temperature
  2. customThe solvent was removed on Rotavapor
  3. additionthe residue was diluted with saturated NaHCO3 solution
  4. extractionextracted with ethyl ether (100 mL×3)
  5. dry with materialCombined extracts were dried over anhydrous Na2SO4
  6. filtrationfiltered through Celite
  7. custompurified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-b24e65191116453a8abde761c4e8fe15
Source dataset
uspto-grants-2006_02
Patent number
US06995284B2

Reaction notes

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