Hydrochloric Acid → 3-Bromo-4-((3S,4R)-3,4-dihydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)-benzamide

HRID 923840Notes

Reaction equation

HRID 923840 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1F)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=1)=[O:6].[NH:23]1[CH2:27][C@@H:26]([OH:28])[C@@H:25]([OH:29])[CH2:24]1.Cl>CS(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[N:23]1[CH2:27][C@@H:26]([OH:28])[C@@H:25]([OH:29])[CH2:24]1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=1)=[O:6]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 13329882(3R,4S)-pyrrolidine-3,4-diolHCID 867025923-bromo-4-fluoro-N-(4-(trifluoromethoxy)phenyl)benzamide

Product 1

HCID 899070193-Bromo-4-((3S,4R)-3,4-dihydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)-benzamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 3-bromo-4-fluoro-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 1.2, 500 mg, 1.32 mmol), (3S,4R)-pyrrolidine-3,4-diol (170 mg, 1.65 mmol) and TEA (369 μL, 2.64 mmol) in DMSO (1322 μL) was stirred at 90° C. for 20 h. The RM was treated with 0.5 M HCl (15 mL) and extracted with EtOAc (30 mL). The aq. phase was back-extracted with EtOAc (2×20 mL) and the combined organic layers were washed with sat. NaHCO3 and brine, and dried over Na2SO4. The crude product was purified by flash chromatography (RediSep® Silica gel column, 40 g, cyclohexane/EtOAc, from 50% to 100% EtOAc) to yield the title compound as a white amorphous solid. UPLC-MS (Condition 3) tR=1.02 min, m/z=461.2-463.1 [M+H]+, m/z=459.1-461.1 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.40 (dd, J=9.90, 4.52 Hz, 2H) 3.67 (dd, J=9.66, 5.26 Hz, 2H) 4.06-4.16 (m, 2H) 4.94 (d, J=4.65 Hz, 2H) 6.86 (d, J=8.80 Hz, 1H) 7.34 (d, J=8.31 Hz, 2H) 7.80-7.91 (m, 3H) 8.13 (d, J=2.20 Hz, 1H) 10.17 (s, 1H).

Workup

  1. extractionextracted with EtOAc (30 mL)
  2. extractionThe aq. phase was back-extracted with EtOAc (2×20 mL)
  3. washthe combined organic layers were washed with sat. NaHCO3 and brine
  4. dry with materialdried over Na2SO4
  5. customThe crude product was purified by flash chromatography (RediSep® Silica gel column, 40 g, cyclohexane/EtOAc, from 50% to 100% EtOAc)

Sources & evidence

ORD record
ord-79931b96f4bf44eba16bbe61e2eac7bd
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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