Lithium hydroxide, monohydrate → (S)-3-(1-cyclohexyl-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)-amino)propan-2-ylcarbamoyl)benzoic acid

HRID 1254385Notes

Reaction equation

HRID 1254385 reaction equation
[CH:1]1([CH2:7][C@H:8]([NH:21][C:22]([C:24]2[CH:25]=[C:26]([CH:31]=[CH:32][CH:33]=2)[C:27]([O:29]C)=[O:28])=[O:23])[CH2:9][N:10]([CH3:20])[C:11]([O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])=[O:12])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.O[Li].O>C1COCC1.O>[CH:1]1([CH2:7][C@H:8]([NH:21][C:22]([C:24]2[CH:25]=[C:26]([CH:31]=[CH:32][CH:33]=2)[C:27]([OH:29])=[O:28])=[O:23])[CH2:9][N:10]([CH3:20])[C:11]([O:13][CH2:14][CH2:15][Si:16]([CH3:17])([CH3:18])[CH3:19])=[O:12])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 67192450(S)-methyl 3-(1-cyclohexyl-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-ylcarbamoyl)benzoate

Product 1

HCID 67190092(S)-3-(1-cyclohexyl-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)-amino)propan-2-ylcarbamoyl)benzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (S)-methyl 3-(1-cyclohexyl-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)-amino)propan-2-ylcarbamoyl)benzoate (1.397 g) and LiOH.H2O (0.430 g, 10 mmol, 5.7 equiv) in THF (50 mL) and H2O (10 mL) was vigorously stirred at rt for 23 h. The reaction mixture was quenched with 2 N HCl (6 mL). After the organic solvent was removed in vacuo, the aqueous phase was extracted with CH2Cl2 (3×) and the combined organic layers were dried over Na2SO4. The crude (S)-3-(1-cyclohexyl-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-ylcarbamoyl)benzoic acid (0.923 g) was used in the next step without further purification. LC-MS (3 min) tR=2.06 min, m/z 485 (M+Na+), 435, 391. 13C NMR (100 MHz, CDCl3) δ 168.45, 166.95, 157.89, 135.27, 132.73, 132.34, 129.95, 128.47, 128.42, 64.25, 52.86, 45.49, 40.59, 34.58, 34.26, 33.77, 33.13, 26.46, 26.23, 26.11, 17.64, −1.61.

Workup

  1. customThe reaction mixture was quenched with 2 N HCl (6 mL)
  2. customAfter the organic solvent was removed in vacuo
  3. extractionthe aqueous phase was extracted with CH2Cl2 (3×)
  4. dry with materialthe combined organic layers were dried over Na2SO4
  5. customThe crude (S)-3-(1-cyclohexyl-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-ylcarbamoyl)benzoic acid (0.923 g) was used in the next step without further purification
  6. customLC-MS (3 min) tR=2.06 min, m/z 485 (M+Na+), 435, 391

Sources & evidence

ORD record
ord-7868d6f3907848c79cdfc4c104722ddf
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

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