Lithium hydroxide, monohydrate → HCID 178426999, compound

HRID 1058438Notes

Reaction equation

HRID 1058438 reaction equation
FC(F)(F)C(O)=O.C[O:9][C:10](=[O:44])/[C:11](/[NH:22][C:23](=[O:43])[C:24]1[C:29]([CH3:30])=[CH:28][C:27]([C:31]([NH:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([OH:41])[CH:36]=2)=[O:32])=[CH:26][C:25]=1[Cl:42])=[CH:12]/[C:13]1[CH:21]=[CH:20][C:16]2[NH:17][N:18]=[N:19][C:15]=2[CH:14]=1.O.[OH-].[Li+]>CO.O1CCCC1.O>[NH:17]1[C:16]2[CH:20]=[CH:21][C:13](/[CH:12]=[C:11](\[NH:22][C:23](=[O:43])[C:24]3[C:29]([CH3:30])=[CH:28][C:27]([C:31]([NH:33][CH2:34][C:35]4[CH:40]=[CH:39][CH:38]=[C:37]([OH:41])[CH:36]=4)=[O:32])=[CH:26][C:25]=3[Cl:42])/[C:10]([OH:44])=[O:9])=[CH:14][C:15]=2[N:19]=[N:18]1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 178499693HCID 178499693, compound

Product 1

HCID 178426999HCID 178426999, compoundYield 61.4%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

A mixture of (Z)-3-(1H-benzotriazol-5-yl)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]propenoic acid methyl ester trifluoroacetate salt (Example 210; 18 mg, 0.028 mmol) and lithium hydroxide monohydrate (6 mg, 0.144 mmol) in methanol/tetrahydrofuran/water (2:2:1; 0.5 mL) was stirred at room temperature for 125 h. After the volatiles were removed under reduced pressure, the residue was taken up in a mixture of chloroform/methanol/water/acetic acid (150:30:10:6) (10 mL) and evaporated to dryness. The crude product was re-suspended in the same solvent mixture (1 mL) and applied to a column of two piggy-backed SepPak Plus® silica gel cartridges that had been pre-washed with chloroform. The column was eluted with in turn with chloroform, chloroform/methanol/water/acetic acid (600:30:10:6), chloroform/methanol/water/acetic acid (300:30:10:6 and chloroform/methanol/water/acetic acid (150:30:10:6). The appropriate fractions were combined, evaporated and lyophilized to furnish (Z)-3-(1H-benzotriazol-5-yl)-2-[[2-chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]-6-methylbenzoyl]amino]propenoic acid (8.7 mg, 61% yield) as a colorless powder.

Workup

  1. customAfter the volatiles were removed under reduced pressure
  2. additionthe residue was taken up in a mixture of chloroform/methanol/water/acetic acid (150:30:10:6) (10 mL)
  3. customevaporated to dryness
  4. washhad been pre-washed with chloroform
  5. washThe column was eluted with in turn with chloroform, chloroform/methanol/water/acetic acid (600:30:10:6), chloroform/methanol/water/acetic acid (300:30:10:6 and chloroform/methanol/water/acetic acid (150:30:10:6)
  6. customevaporated

Sources & evidence

ORD record
ord-0bad6d7586ed4a1f83972234b824fe07
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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