Citric Acid → HCID 131732317, compound

HRID 2272363Notes

Reaction equation

HRID 2272363 reaction equation
[Li+].[BH4-].[Br:3][C:4]1[C:13]([F:14])=[CH:12][C:11]([N:15]([C:20]2[C:39]([CH:40]3[CH2:42][CH2:41]3)=[CH:38][C:23]3[C:24]([C:34](=[O:37])[NH:35][CH3:36])=[C:25]([C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=4)[O:26][C:22]=3[CH:21]=2)[S:16]([CH3:19])(=[O:18])=[O:17])=[CH:10][C:5]=1[C:6](OC)=[O:7].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.CO>[Br:3][C:4]1[C:5]([CH2:6][OH:7])=[CH:10][C:11]([N:15]([C:20]2[C:39]([CH:40]3[CH2:42][CH2:41]3)=[CH:38][C:23]3[C:24]([C:34]([NH:35][CH3:36])=[O:37])=[C:25]([C:27]4[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=4)[O:26][C:22]=3[CH:21]=2)[S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][C:13]=1[F:14]

Participants

6

Reactant 3

HCID 311Citric AcidHCID 4148881Lithium borohydrideHCID 131732316HCID 131732316, compound

Product 1

HCID 131732317HCID 131732317, compoundYield 97.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of LiBH4 (1.018 mL, 2M) in THF was added dropwise to a solution of methyl 2-bromo-5-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)-3-fluorobenzoate (430 mg, 0.679 mmol) in MeOH (0.5 mL) and THF (5.0 mL) at 0° C. After 0.5 h, citric acid (4.0 mL, 5% wt) was added to the mixture. The organic solvent was then removed under reduced pressure. The residue was diluted with DCM (10 mL) and washed with saturated aqueous NaHCO3, brine, dried over Na2SO4, filtered and concentrated to give 6-(N-(4-bromo-3-fluoro-5-(hydroxymethyl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (400 mg, 97% yield) as white solid. The crude was used for next step without more purification. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.57 (br. s., 1H), 0.71-0.88 (m, 2H), 0.93-1.06 (m, 1H), 1.96-2.02 (m, 1H), 2.63 (t, J=6.1 Hz, 1H), 2.96 (d, J=4.8 Hz, 3H), 3.25 (s, 3H), 4.67 (d, J=5.6 Hz, 2H), 5.96 (d, J=4.8 Hz, 1H), 7.08-7.21 (m, 3H), 7.31 (s, 1H), 7.42 (s, 1H), 7.56 (s, 1H), 7.82 (dd, J=8.7, 5.3 Hz, 2H). LCMS (m/z, ES+)=605, 607 (M+H+).

Workup

  1. customThe organic solvent was then removed under reduced pressure
  2. additionThe residue was diluted with DCM (10 mL)
  3. washwashed with saturated aqueous NaHCO3, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-a2ec772117d34729b8842b600ecf2a1f
Source dataset
uspto-grants-2015_09
Patent number
US09119868B2

Reaction notes

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