Lithium hydroxide, monohydrate → (R)-3-(1-Naphthamido)-2,3-dihydro-1H-indene-5-carboxylic acid

HRID 1193289Notes

Reaction equation

HRID 1193289 reaction equation
O[Li].O.[C:4]1([C:14]([NH:16][C@H:17]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]([O:28]C)=[O:27])[CH:24]=3)[CH2:19][CH2:18]2)=[O:15])[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[CH:6][CH:5]=1>O.CO>[C:4]1([C:14]([NH:16][C@H:17]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]([OH:28])=[O:27])[CH:24]=3)[CH2:19][CH2:18]2)=[O:15])[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrate2×HCID 66799274(R)-Methyl 3-(1-naphthamido)-2,3-dihydro-1H-indene-5-carboxylate

Product 1

HCID 66799120(R)-3-(1-Naphthamido)-2,3-dihydro-1H-indene-5-carboxylic acidYield 96%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

LiOH.H2O (0.272 g, 3.62 mmol, 5 eq) dissolved in water (0.6 ml) was added dropwise to a cooled (0° C.) solution of (R)-methyl 3-(1-naphthamido)-2,3-dihydro-1H-indene-5-carboxylate (B-36) (0.25 g, 0.724 mmol, 1 eq) in MeOH (3 ml), and the resulting mixture was stirred for 16 h at RT. After monitoring by TLC, further LiOH.H2O (0.272 g, 3.62 mmol, 5 eq) was metered in, and the reaction mixture was heated to 40° C. and stirred for 1 hour. Then the reaction solution was concentrated under reduced pressure, the residue was taken up in water and diethyl ether, and the phases were separated. The aqueous phase was acidified with 1 M HCl and extracted with ethyl acetate. The organic phase was dried over magnesium sulfate and concentrated under reduced pressure. Yield: 96% (0.23 g)

Workup

  1. additionwas added dropwise to
  2. temperaturewas heated to 40° C.
  3. stirringstirred for 1 hour
  4. concentrationThen the reaction solution was concentrated under reduced pressure
  5. customdiethyl ether, and the phases were separated
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic phase was dried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ba9d3f76ee7a499d8e5c1e38b5e9a10e
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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