Lithium Hydroxide → 4-[(2R)-2-({[(2R)-2-(6-amino-3-pyridinyl)-2-hydroxyethyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid

HRID 896903Notes

Reaction equation

HRID 896903 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C@@H:8]([OH:32])[CH2:9][NH:10][CH2:11][C@H:12]2[CH2:21][CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:22]4[CH:31]=[CH:30][C:25]([C:26]([O:28]C)=[O:27])=[CH:24][CH:23]=4)[CH:18]=3)[O:13]2)=[CH:4][CH:3]=1.[OH-].[Li+]>C1COCC1.CO>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C@@H:8]([OH:32])[CH2:9][NH:10][CH2:11][C@H:12]2[CH2:21][CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:22]4[CH:23]=[CH:24][C:25]([C:26]([OH:28])=[O:27])=[CH:30][CH:31]=4)[CH:18]=3)[O:13]2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 59118232methyl 4-[(2R)-2-({[(2R)-2-(6-amino-3-pyridinyl)-2-hydroxyethyl]amino}-methyl)-3,4-dihydro-2H-chromen-6-yl]benzoate

Product 1

HCID 101368584-[(2R)-2-({[(2R)-2-(6-amino-3-pyridinyl)-2-hydroxyethyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acidYield 28%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-[(2R)-2-({[(2R)-2-(6-amino-3-pyridinyl)-2-hydroxyethyl]amino}-methyl)-3,4-dihydro-2H-chromen-6-yl]benzoate (Example 381, 40 mg, 0.1 mmol) in THF (2 mL) and methanol (2 mL) was added 2 M aq. lithium hydroxide (0.5 mL, 1 mmol). The mixture was stirred at room temperature for 18 hours and then concentrated in vacuo. Prep. HPLC of the residue afforded 10.8 mg (28%) of the desired product. The product had: 1H NMR (CDCl3, δ): 7.96 (d, J=8.2 Hz, 2 H), 7.90 (d, J=2.2 Hz, 1 H), 7.49-7.56 (m, 3 H), 7.32-7.39 (m, 2 H), 6.82 (d, J=9.0 Hz, 1 H), 6.59 (d, J=8.6 Hz, 1 H), 4.70 (dd, J=8.3, 4.4 Hz, 1 H), 4.14-4.23 (m, 1 H), 2.75-3.02 (m, 6 H), 1.99-2.10 (m, 1 H), 1.70-1.85 (m, 1 H); mass spectroscopy gave m/z=420.2 [M+H]+ (calc'd exact mass for C24H25N3O4=419.2).

Workup

  1. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a40bbfd666f94f42bf4e7780ce2518d6
Source dataset
uspto-grants-2005_07
Patent number
US06919371B2

Reaction notes

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