Lithium hydroxide, monohydrate → HCID 57122299, compound

HRID 1197699Notes

Reaction equation

HRID 1197699 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH3:13])([CH3:12])[C@@H:9]([OH:14])[C@H:8]([NH:15][C:16]([NH:18][C:19]3[CH:20]=[C:21]([CH2:25][C:26]([O:28]C)=[O:27])[CH:22]=[CH:23][CH:24]=3)=[O:17])[C:7]=2[CH:30]=1)#[N:2].O.[OH-].[Li+]>CO>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH3:13])([CH3:12])[C@@H:9]([OH:14])[C@H:8]([NH:15][C:16]([NH:18][C:19]3[CH:20]=[C:21]([CH2:25][C:26]([OH:28])=[O:27])[CH:22]=[CH:23][CH:24]=3)=[O:17])[C:7]=2[CH:30]=1)#[N:2]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86747473HCID 86747473, compound

Product 1

HCID 57122299HCID 57122299, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (3S-trans)-3-[[[(6-cyano-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl) amino]carbonyl]amino]-benzeneacetic acid, methyl ester (0.7 g, 1.7 mmol, title compound from Example 24) in methanol (15 ml) under argon was treated with lithium hydroxide hydrate (0.14 g, 3.4 mmol) and the reaction was stirred at room temperature for 16 hours. More lithium hydroxide (two equivalent) was added and the reaction mixture was stirred for 48 hours. It was concentrated in vacuo and the residue was diluted with water (50 ml) and extracted with ethyl acetate. Organic layer was discarded and aqueous layer was acidified to pH~1 with 10% hydrochloric acid and extracted with ethyl acetate (3×100 ml). It was washed with water (100 ml) and concentrated in vacuo. The residue was flash chromatographed on silica gel eluting with methylene chloride/methanol/acetic acid (1800:200:5) to give (3S-trans)-3-[[[(6-cyano-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl)amino]carbonyl]amino]benzeneacetic acid as a colorless solid (0.5 g, 73.9%), m.p. 135-138° C. (with foaming): 1H NMR (DMSO-d6) δ 8.76 (s, 2 H), 7.62 (m, 2 H), 7.42 (m, 2 H), 7.25 (m, 2 H), 6.96 (d, J=8.3 Hz, 1 H), 6.90 (d, J=7.0 Hz, 1 H), 6.70 (d, J=8.2 Hz, 1 H), 4.77 (m, 2 H), 3.76 (m, 2 H), 1.51 (s, 3 H), 1.28 (s, 3 H); 13C NMR (CDCl3) 172.8, 156.3, 155.9, 140.3, 135.6, 132.7, 132.4, 128.6, 126.0, 122.4, 119.1, 118.8, 117.9, 116.2, 102.7, 80.3, 71.6, 49.4, 26.5, 18.9; IR (KBr) 1132.1, 1267.2, 1491.3, 1559.3, 1611.2, 1659.3, 1713.2, 2228.1, 2980.1, 3379.0 cm-1 ; [α]25D=-6.7° (c=0.683, DMF).

Sources & evidence

ORD record
ord-c4dfbcb010054993ae81db6dfa0f638f
Source dataset
uspto-grants-1994_01
Patent number
US05276168

Reaction notes

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