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

HRID 1253660Notes

Reaction equation

HRID 1253660 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([N:11]([C@H:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([C:22]([O:24]C)=[O:23])[CH:20]=2)[CH2:15][CH2:14]1)[CH3:12])(=[O:10])=[O:9].O[Li].O>CO.C1COCC1.O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([N:11]([C@H:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([C:22]([OH:24])=[O:23])[CH:20]=2)[CH2:15][CH2:14]1)[CH3:12])(=[O:9])=[O:10]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 59505532(R)-Methyl 3-(2-chloro-N-methylphenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylate

Product 1

HCID 59505351(R)-3-(2-Chloro-N-methylphenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylic acidYield 58%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a cooled (0° C.) solution of (R)-methyl 3-(2-chloro-N-methylphenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylate (C-16) (840 mg, 2.216 mmol, 1.0 eq.) in MeOH:THF (1:1, 20 ml) was added dropwise a solution of LiOH.H2O (185 mg, 4.433 mmol, 2.0 eq.) in water (10 ml) and the reaction mixture was stirred at RT for 3 h. After completion of the reaction (monitored by TLC), the reaction mixture was concentrated to dryness and diluted with water (20 ml) and washed with ethyl acetate (20 ml). The aqueous layer was acidified to pH≈3 using 1N HCl and then extracted with methylene chloride (2×50 ml). The combined organic layers were dried over anhydrous Na2SO4 and concentrated to afford the desired product as an off-white solid. Yield: 58% (470 mg, 1.2876 mmol).

Workup

  1. customAfter completion of the reaction (monitored by TLC)
  2. concentrationthe reaction mixture was concentrated to dryness
  3. additiondiluted with water (20 ml)
  4. washwashed with ethyl acetate (20 ml)
  5. extractionextracted with methylene chloride (2×50 ml)
  6. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-a81f7a5d3b0b4106a6eee065232d9c11
Source dataset
uspto-grants-2013_06
Patent number
US08455475B2

Reaction notes

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