Acetic Acid → 4-((R)-2-Hydroxymethyl-pyrrolidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 545329Notes

Reaction equation

HRID 545329 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:15]1[CH2:19][CH2:18][CH2:17][C@@H:16]1[CH2:20][OH:21].C(O)(=O)C.C(=O)([O-])[O-].[Na+].[Na+]>CCO.ClCCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:15]2[CH2:19][CH2:18][CH2:17][C@@H:16]2[CH2:20][OH:21])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 10340Sodium CarbonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 2724541Prolinol, (R)-

Product 1

HCID 671332864-((R)-2-Hydroxymethyl-pyrrolidin-1-yl)-piperidine-1-carboxylic acid tert-butyl esterYield 90.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 702EthanolSolvent

Procedure

A solution of 5.98 g (30.0 mmol) of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester and 3.55 ml=3.64 g (36.0 mmol) of (R)-(−)-pyrrolidin-2-yl-methanol in 60.0 ml of EtOH was treated with 60.0 ml of 1,2-dichloroethane, followed by 4.50 ml (36 mmol) of borane-pyridine complex (8 molar). Then, 4.46 ml=4.68 g (78.0 mmol) of acetic acid was added to this solution. After stirring at RT for 16 hours, the reaction mixture was poured into crashed ice; then, the pH was adjusted to 9-10 with sodium carbonate solution and the mixture was extracted twice with EtOAc; the combined organic phases were washed with water, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 8:2) to give 7.69 g (90%) of the title compound as light yellow oil. MS: 285.1 (MH+).

Workup

  1. additionthe reaction mixture was poured
  2. extractionthe mixture was extracted twice with EtOAc
  3. washthe combined organic phases were washed with water
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 8:2)

Sources & evidence

ORD record
ord-573f88dabac14df88f31a44abb2eff6b
Source dataset
uspto-grants-2011_05
Patent number
US07935707B2

Reaction notes

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