Methanol → 1-(tert-butoxycarbonyl)-4-((1-trityl-1H-imidazol-4-yl)methyl)piperidine-4-carboxylic acid

HRID 216078Notes

Reaction equation

HRID 216078 reaction equation
[C:1]([N:20]1[CH:24]=[C:23]([CH2:25][C:26]2([C:39]([O:41]CC)=[O:40])[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]2)[N:22]=[CH:21]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1COCC1.CO.[Li+].[OH-]>O>[C:35]([O:34][C:32]([N:29]1[CH2:28][CH2:27][C:26]([CH2:25][C:23]2[N:22]=[CH:21][N:20]([C:1]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:24]=2)([C:39]([OH:41])=[O:40])[CH2:31][CH2:30]1)=[O:33])([CH3:38])([CH3:36])[CH3:37]

Participants

6

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 670377361-tert-butyl 4-ethyl 4-((1-trityl-1H-imidazol-4-yl)methyl)piperidine-1,4-dicarboxylate

Product 1

HCID 689935991-(tert-butoxycarbonyl)-4-((1-trityl-1H-imidazol-4-yl)methyl)piperidine-4-carboxylic acidYield 86.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 1-tert-butyl 4-ethyl 4-((1-trityl-1H-imidazol-4-yl)methyl)piperidine-1,4-dicarboxylate from step A (330 mg, 0.57 mmol) in 1:1:2 THF:MeOH:H2O (10 mL) was added LiOH (136 mg, 5.7 mmol). The mixture was refluxed until LCMS showed complete conversion to product, then concentrated under vacuum, dissolved in water (3 mL), neutralized to pH 5-6 with aq. NaHSO4, and extracted with ethyl acetate (3×10 mL). The combined organic phases were washed with brine, dried over Na2SO4, and concentrated under vacuum to give the title compound (273 mg, 86%). MS (ES+) [M+H]+=552.2.

Workup

  1. temperatureThe mixture was refluxed until LCMS
  2. concentrationconcentrated under vacuum
  3. dissolutiondissolved in water (3 mL)
  4. extractionextracted with ethyl acetate (3×10 mL)
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-b83a241f38e447beac2e0df786f1754c
Source dataset
uspto-grants-2012_06
Patent number
US08193202B2

Reaction notes

Loading…