1-Hydroxybenzotriazole → HCID 46840706, compound

HRID 1255022Notes

Reaction equation

HRID 1255022 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([NH:10][CH:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:12]([OH:14])=[O:13])[CH:6]=[CH:7][C:8]=1[CH3:9].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[N:40]12[CH2:47][CH2:46][CH:43]([CH2:44][CH2:45]1)[C@@H:42](O)[CH2:41]2>C(#N)C>[N:40]12[CH2:47][CH2:46][CH:43]([CH2:44][CH2:45]1)[C@@H:42]([O:13][C:12](=[O:14])[CH:11]([NH:10][C:5]1[CH:6]=[CH:7][C:8]([CH3:9])=[C:3]([F:2])[CH:4]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[CH2:41]2

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 914043-Quinuclidinol, (-)-HCID 67425700(3-Fluoro-4-methyl-phenylamino)-phenyl-acetic acid hydrochloride

Product 1

HCID 46840706HCID 46840706, compoundYield 100.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(3-Fluoro-4-methyl-phenylamino)-phenyl-acetic acid hydrochloride (I48) (250 mg, 0.84 mmol), 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate (V) (321 mg, 0.84 mmol), and HOBT (129 mg, 0.84 mmol) are dissolved in acetonitrile (6 mL). DIPEA (0.29 mL, 1.69 mmol) is added, followed by (R)-quinuclidin-3-ol (215 mg, 1.69 mmol) and the resulting yellow solution is stirred at RT overnight (Conversion complete by UPLC/MS-UV). MeCN is evaporated, the residue is dissolved in EtOAc and washed with sat. NaHCO3, water and brine. The organic layer is recovered, dried over Na2SO4, filtered and evaporated. The crude compound is purified by filtration through a pad of silica using DCM/MeOH=9/1 as the eluent to obtain the title compound as a yellow oil (311 mg, quantitative yield, mixture of diastereoisomers).

Workup

  1. customMeCN is evaporated
  2. dissolutionthe residue is dissolved in EtOAc
  3. washwashed with sat. NaHCO3, water and brine
  4. customThe organic layer is recovered
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. filtrationThe crude compound is purified by filtration through a pad of silica

Sources & evidence

ORD record
ord-8d5535bbfcf749c58ff47c000af01c0a
Source dataset
uspto-grants-2013_06
Patent number
US08455646B2

Reaction notes

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