1-Hydroxybenzotriazole → HCID 59401203, compound

HRID 76997Notes

Reaction equation

HRID 76997 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:23])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([NH:12][CH:13]([C:20]([OH:22])=[O:21])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:7]=1)[CH3:3].C1C=CC2N(O)N=NC=2C=1.[N:34]12[CH2:41][CH2:40][CH:37]([CH2:38][CH2:39]1)[C@@H:36](O)[CH2:35]2.CCN(C(C)C)C(C)C>C1COCC1>[CH2:2]([O:4][C:5](=[O:23])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([NH:12][CH:13]([C:20]([O:22][C@@H:36]2[CH:37]3[CH2:40][CH2:41][N:34]([CH2:39][CH2:38]3)[CH2:35]2)=[O:21])[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:7]=1)[CH3:3]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 914043-Quinuclidinol, (-)-HCID 674258513-[(Carboxy-phenyl-methyl)-amino]-benzoic acid ethyl ester hydrochloride

Product 1

HCID 59401203HCID 59401203, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-[(Carboxy-phenyl-methyl)-amino]-benzoic acid ethyl ester hydrochloride (I66) (161 mg, 0.48 mmol), 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (218 mg, 0.57 mmol), and HOBT (88 mg, 0.57 mmol) are dissolved in dry THF (10 mL). (R)-Quinuclidin-3-ol (61.0 mg, 0.48 mmol) and DIPEA (0.17 mL, 0.96 mmol) are added and the mixture is stirred under inert atmosphere overnight. THF is evaporated and the crude residue is dissolved in EtOAc and washed with sat. NaHCO3, water and brine. The recovered organic layer is dried (Na2SO4), filtered and evaporated. The crude is purified by flash chromatography (DCM/MeOH=95/5) to afford the title compound as a yellow oil (154 mg, 79% yield, mixture of diastereoisomers).

Workup

  1. customTHF is evaporated
  2. dissolutionthe crude residue is dissolved in EtOAc
  3. washwashed with sat. NaHCO3, water and brine
  4. dry with materialThe recovered organic layer is dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude is purified by flash chromatography (DCM/MeOH=95/5)

Sources & evidence

ORD record
ord-24e41b968b6e4d02a19ca144f829c259
Source dataset
uspto-grants-2014_09
Patent number
US08835682B2

Reaction notes

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