Hydrochloric Acid → 1-[1,4']Bipiperidinyl-1'-yl-2-(di-tert-butoxycarbonylamino)-3-(4-hydroxy-piperidin-1-yl)-propan-1-one

HRID 2250202Notes

Reaction equation

HRID 2250202 reaction equation
CO[C:3](=[O:28])[CH:4]([N:13]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([OH:12])[CH2:8][CH2:7]1.O.[OH-].[Li+].Cl.[NH:33]1[CH2:38][CH2:37][CH:36]([N:39]2[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]2)[CH2:35][CH2:34]1.C(N(CC)CC)C.[PH2](Cl)=O>CO.O>[N:39]1([CH:36]2[CH2:37][CH2:38][N:33]([C:3](=[O:28])[CH:4]([N:13]([C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[C:14]([O:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[O:15])[CH2:5][N:6]3[CH2:7][CH2:8][CH:9]([OH:12])[CH2:10][CH2:11]3)[CH2:34][CH2:35]2)[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 786071,4'-BipiperidineHCID 168937Lithium hydroxide, monohydrateHCID 588645182-(Di-tert-butoxycarbonylamino)-3-(4-hydroxy-piperidin-1-yl)-propionic acid methyl esterHCID 178527016HCID 178527016, compound

Product 1

HCID 211020511-[1,4']Bipiperidinyl-1'-yl-2-(di-tert-butoxycarbonylamino)-3-(4-hydroxy-piperidin-1-yl)-propan-1-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(di-tert-butoxycarbonylamino)-3-(4-hydroxy-piperidin-1-yl)-propionic acid methyl ester (1.0 g, 2.5 mmol) in methanol (6 mL) was added a solution of lithium hydroxide monohydrate (400 mg, 3.9 equiv) in water (1 mL). The reaction was stirred 6 h, cooled to 0° C., neutralized with concentrated hydrochloric acid, and concentrated. The crude acid was used without purification. The crude acid was suspended in methylene chloride (25 mL), treated with a few drops of methanol to aid in dissolving the acid, and cooled to 0° C. The resulting suspension was treated sequentially with 4-piperidyl-piperidine (0.53 g, 1.25 equiv), triethylamine (0.70 mL, 2.0 equiv), and bis-2-oxo-3-oxazolidinyl)phoshinic chloride (0.80 g, 1.25 equiv). The reaction was allowed to warm to room temperature overnight. The reaction was concentrated and then purified by Prep HPLC to afford 310 mg (23%, 2 steps). Mass spec.: 539.49 (MH)+.

Workup

  1. concentrationconcentrated
  2. customThe crude acid was used without purification
  3. additiontreated with a few drops of methanol
  4. dissolutionin dissolving the acid
  5. temperatureto warm to room temperature overnight
  6. concentrationThe reaction was concentrated
  7. custompurified by Prep HPLC
  8. customto afford 310 mg (23%, 2 steps)

Sources & evidence

ORD record
ord-9be18d02189b406bbc8a4161faa620f7
Source dataset
uspto-grants-2008_01
Patent number
US07314883B2

Reaction notes

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