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

HRID 1177724Notes

Reaction equation

HRID 1177724 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.[PH2](Cl)=O>CO.O.C(N(CC)CC)C>[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 5

HCID 313Hydrochloric AcidHCID 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 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8471TriethylamineSolvent

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. 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-c651685d1b8a46f592f6a75bb64347c5
Source dataset
uspto-grants-2010_11
Patent number
US07842808B2

Reaction notes

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