Tetrahydrofuran → HCID 67972328, compound

HRID 1626291Notes

Reaction equation

HRID 1626291 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([F:17])[CH:13]([NH2:18])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1COCC1.Br[CH2:25][CH2:26][CH2:27][CH2:28][C:29](Cl)=[O:30].CCN(CC)CC>CCOC(C)=O>[F:17][CH:14]1[CH2:15][CH2:16][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[CH2:12][CH:13]1[N:18]1[CH2:25][CH2:26][CH2:27][CH2:28][C:29]1=[O:30]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 5211735-Bromovaleryl chlorideHCID 42609256Benzyl 3-amino-4-fluoropiperidine-1-carboxylate

Product 1

HCID 67972328HCID 67972328, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-amino-4-fluoro-piperidine-1-carboxylic acid benzylester 37.1 (1.0 eq) in THF (40 eq) cooled in an ice water bath was added 5-bromo-pentanoyl chloride (1 eq) and Et3N (2 eq) dropwise. The reaction mixture was warmed to RT and stirred for 2 h, diluted with EtOAc and washed with aq 5% citric acid (500 mL), dried over Na2SO4, concentrated in vacuo to afford an oil. The oil was purified by flash chromatography (10% EtOAc/Hexane to 100% EtOAc) to provide the amide intermediate which was dissolved in THF (30 mL) and treated with sodium hydride (60% in mineral oil, 5 eq) at 65° C. for 16 h. The reaction mixture cooled in an ice water bath and methanol added dropwise, diluted with EtOAc and washed with aq. 5% citric acid, dried over Na2SO4 and concentrated to afford an oil. The oil was purified by flash chromatography (EtOAc to 5% CH3OH/EtOAc) to provide compound 37.2 as a colorless oil (62% yield). EIMS (m/z): calcd. for C18H23FN2O3 (M++1) 335.39. Found 335.00.

Workup

  1. washwashed with aq 5% citric acid (500 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customto afford an oil
  5. customThe oil was purified by flash chromatography (10% EtOAc/Hexane to 100% EtOAc)

Sources & evidence

ORD record
ord-e146d578567d4fe3a2c35ff63fc82fe4
Source dataset
uspto-grants-2014_07
Patent number
US08785440B2

Reaction notes

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