Hydrochloric Acid → (S)-4-(2-(4-(tert-butyl)benzamido)-3-methoxy-3-oxopropyl)benzoic acid

HRID 1775798Notes

Reaction equation

HRID 1775798 reaction equation
[C:1]([C:5]1[CH:29]=[CH:28][C:8]([C:9]([NH:11][C@H:12]([C:24]([O:26][CH3:27])=[O:25])[CH2:13][C:14]2[CH:23]=[CH:22][C:17]([C:18]([O:20]C)=[O:19])=[CH:16][CH:15]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].O.[OH-].[Li+].Cl>O1CCOCC1.O>[C:1]([C:5]1[CH:29]=[CH:28][C:8]([C:9]([NH:11][C@H:12]([C:24]([O:26][CH3:27])=[O:25])[CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:18]([OH:20])=[O:19])=[CH:22][CH:23]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 86689654(S)-methyl 4-(2-(4-(tert-butyl)benzamido)-3-methoxy-3-oxopropyl)benzoate

Product 1

HCID 86689655(S)-4-(2-(4-(tert-butyl)benzamido)-3-methoxy-3-oxopropyl)benzoic acidYield 69%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Prepared using General Procedure 4: To a stirred solution of (S)-methyl 4-(2-(4-(tert-butyl)benzamido)-3-methoxy-3-oxopropyl)benzoate (316.6 mg, 0.79 mmol) in dioxane (15 mL) and water (1 mL) at 0° C. was added lithium hydroxide monohydrate (93.52 mg, 2.23 mmol). After 2 h, the solution was neutralized with 1 M HCl to pH 7.0. The mixture was partitioned between DCM (15 mL) and saturated aqueous NaHCO3 (10 mL). The organic layer was washed with saturated aqueous NaHCO3 (3×10 mL) and brine (10 mL). The organic layer was dried over MgSO4 and concentrated to afford 208 mg (69%) of (S)-4-(2-(4-(tert-butyl)benzamido)-3-methoxy-3-oxopropyl)benzoic acid, INT-1. LCMS-ESI (m/z) calculated for C22H25NO5: 383.2. found 384.1 [M+H]+, tR=2.13 min. (Method 1). 1H NMR (400 MHz, DMSO) δ 12.86 (s, 1H), 8.80 (d, J=8.0 Hz, 1H), 7.87-7.78 (m, 2H), 7.75-7.65 (m, 2H), 7.50-7.35 (m, 4H), 4.72 (ddd, J=10.3, 8.0, 5.1 Hz, 1H), 3.65 (s, 3H), 3.28-3.05 (m, 2H), 1.29 (s, 9H). 13C NMR (101 MHz, DMSO) δ 173.00, 167.21, 166.29, 154.39, 143.10, 130.85, 129.34, 129.27, 129.21, 129.03, 127.21, 125.39, 125.10, 53.75, 52.04, 34.64, 30.92, 30.88.

Workup

  1. customPrepared
  2. customThe mixture was partitioned between DCM (15 mL) and saturated aqueous NaHCO3 (10 mL)
  3. washThe organic layer was washed with saturated aqueous NaHCO3 (3×10 mL) and brine (10 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-5e449739a4d444dd9a5eaf3ea39417f3
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

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