Tetrahydrofuran → 4-Benzyloxycarbonylamino-4-hydroxymethyl piperidine-1-carboxylic acid tert-butyl ester

HRID 39699Notes

Reaction equation

HRID 39699 reaction equation
O1CCCC1.[CH2:6]([O:13][C:14]([NH:16][C:17]1([C:30](O)=[O:31])[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1)=[O:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(Cl)(=O)OCC.[BH4-].[Na+]>O.C(OCC)(=O)C.C(N(CC)CC)C>[CH2:6]([O:13][C:14]([NH:16][C:17]1([CH2:30][OH:31])[CH2:18][CH2:19][N:20]([C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])[CH2:21][CH2:22]1)=[O:15])[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 10928Ethyl chloroformateHCID 27566404-(((Benzyloxy)carbonyl)amino)-1-(tert-butoxycarbonyl)piperidine-4-carboxylic acidHCID 4311764Sodium borohydride

Product 1

HCID 667417704-Benzyloxycarbonylamino-4-hydroxymethyl piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-15 °C

Procedure

To 20 mL of a tetrahydrofuran suspension containing 1.0 g of 4-(((benzyloxy)carbonyl)amino)-1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid, 0.41 mL of triethylamine was added at room temperature, then the mixture cooled to −15° C., and thereto was added dropwise 0.28 mL of ethyl chlorocarbonate. The reaction mixture was stirred at 5 to 10° C. for 1 hour. Thereto were added 0.11 g of sodium borohydride and 3 mL of water, and the mixture was stirred at room temperature for 1 hour, and stood still overnight. The reaction mixture was added with ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, and the resultant solution was washed with water and an aqueous saturated sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to obtain 0.55 g of a colorless oily substance, tert-butyl 4-(((benzyloxy)carbonyl)amino)-4-(hydroxymethyl)piperidine-1-carboxylate.

Workup

  1. additionwas added at room temperature
  2. stirringthe mixture was stirred at room temperature for 1 hour
  3. waitstood still overnight
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washthe resultant solution was washed with water
  7. dry with materialan aqueous saturated sodium chloride solution and dried over anhydrous magnesium sulfate
  8. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-46a257f0bf9141ecbb1657d9630fbdf0
Source dataset
uspto-grants-2013_09
Patent number
US08524738B2

Reaction notes

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