tert-Butyl 4-oxopiperidine-1-carboxylate → HCID 58997385, compound

HRID 1716902Notes

Reaction equation

HRID 1716902 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C:9](=[O:17])[C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[CH:5]=[CH:4][CH:3]=1.[C:18]([N:25]1[CH2:30][CH2:29][C:28](=O)[CH2:27][CH2:26]1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:21]([O:20][C:18]([N:25]1[CH2:30][CH2:29][CH:28]([NH:1][C:2]2[CH:3]=[CH:4][CH:5]=[C:6]([NH:8][C:9](=[O:17])[C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)[N:7]=2)[CH2:27][CH2:26]1)=[O:19])([CH3:24])([CH3:22])[CH3:23]

Participants

5

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 58997363HCID 58997363, compound

Product 1

HCID 58997385HCID 58997385, compoundYield 90.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Place N-(6-aminopyridin-2-yl)-4-fluorobenzamide (Preparation 37) (2 g, 8.3 mmol) and 1-boc-4-piperidone (15.0 g, 83 mmol) in 1,2-dichloroethane (20 mL). Stir for 1 hr. then add sodium triacetoxyborohydride (4.38 g, 20.8 mmol). After stirring for 36 hr., quench with 1 N NaOH and dilute with CH2Cl2. Separate and extract the aqueous layer twice with CH2Cl2, combine organics, dry over MgSO4, and concentrate. Take up the residue in CH2Cl2, and place on two 10 g SCX columns. Wash the columns successively with CH2Cl2 and then with methanol. Elute the product with 2M NH3 in methanol. Concentrate and chromatograph on silica gel, eluting with a gradient of 0-10% (2M NH3 in methanol) in CH2Cl2) to give the title intermediate 3.11 g (90%): mass spectrum (ion spray): m/z 415.4 (M+1); mp 82.7° C.

Workup

  1. stirringAfter stirring for 36 hr
  2. custom, quench with 1 N NaOH
  3. additiondilute with CH2Cl2
  4. customSeparate
  5. extractionextract the aqueous layer twice with CH2Cl2
  6. dry with materialdry over MgSO4
  7. concentrationconcentrate
  8. washWash the columns successively with CH2Cl2
  9. washElute the product with 2M NH3 in methanol
  10. concentrationConcentrate
  11. washchromatograph on silica gel, eluting with a gradient of 0-10% (2M NH3 in methanol) in CH2Cl2)

Sources & evidence

ORD record
ord-61ff6342f2d14d78ad9576eb600ce317
Source dataset
uspto-grants-2010_09
Patent number
US07803813B2

Reaction notes

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