Hydrochloric Acid → (1R,2R)-3-((2-(4-cyanophenyl)-5'-fluoro-2-isopropyl-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)methyl)benzoic acid

HRID 1805312Notes

Reaction equation

HRID 1805312 reaction equation
C[O:2][C:3](=[O:35])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][N:11]2[C:19]3[C:14](=[CH:15][C:16]([F:20])=[CH:17][CH:18]=3)[C@:13]3([CH2:22][C@:21]3([C:26]3[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][CH:27]=3)[CH:23]([CH3:25])[CH3:24])[C:12]2=[O:34])[CH:5]=1.[OH-].[Na+].Cl>O1CCCC1.O.C(OCC)(=O)C>[C:32]([C:29]1[CH:28]=[CH:27][C:26]([C@@:21]2([CH:23]([CH3:25])[CH3:24])[C@@:13]3([C:14]4[C:19](=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=4)[N:11]([CH2:10][C:6]4[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=4)[C:3]([OH:35])=[O:2])[C:12]3=[O:34])[CH2:22]2)=[CH:31][CH:30]=1)#[N:33]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 67235156(1R,2R)-methyl-3-((2-(4-cyanophenyl)-5'-fluoro-2-isopropyl-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)methyl)benzoate

Product 1

HCID 67232699(1R,2R)-3-((2-(4-cyanophenyl)-5'-fluoro-2-isopropyl-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)methyl)benzoic acidYield 59.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (1S,2S) and (1R,2R)-methyl-3-((2-(4-cyanophenyl)-5′-fluoro-2-isopropyl-2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)methyl)benzoate (500 mg, 1.1 mmol) in tetrahydrofuran (10 mL) was added 30% sodium hydroxide in water (3 mL) at room temperature and the mixture was stirred at that temperature for 16 hours. The mixture was neutralized with 2 N aqueous hydrochloric acid solution, diluted with ethyl acetate (50 mL), washed with water, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% trifluoro-acetic acid in water) afforded the title compound (270 mg, 59.5%) as a white solid: LC/MS m/e calcd. for C28H23FN2O3: 454, observed (M+H)+: 455.2 1H NMR (400 MHz, MeOD-d4) δppm 7.97 (s, 1 H), 7.94 (d, J=7.83 Hz, 1 H), 7.85 (dd, J=7.96, 1.64 Hz, 1 H), 7.67 (dd, J=7.96, 1.39 Hz, 1 H), 7.61 (d, J=7.58 Hz, 1 H), 7.48 (q, I=7.83 Hz, 2 H), 6.74-6.86 (m, 3 H), 5.28 (d, I=15.92 Hz, 1 H), 5.17 (dd, J=8.72, 2.40 Hz, 1 H), 4.97 (d, J=16.17 Hz, 1 H), 3.04 (dt, J=13.64, 6.82 Hz, 1 H), 2.23-2.28 (m, 1 H), 2.20-2.23 (m, 1 H), 0.92 (d, J=7.07 Hz, 3 H), 0.81 (d, J=6.82 Hz, 3 H).

Workup

  1. washwashed with water
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customPurification by waters

Sources & evidence

ORD record
ord-49a06a06017c4d7bac9a0a5fe89429af
Source dataset
uspto-grants-2013_01
Patent number
US08354443B2

Reaction notes

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