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

HRID 1591879Notes

Reaction equation

HRID 1591879 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].[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 5360545SodiumHCID 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 (P reparation 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 triacetoxyborohydrlde (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 colulmns. 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-acab2365f9d44bb3ba083852c9662809
Source dataset
uspto-grants-2007_11
Patent number
US07291632B2

Reaction notes

Loading…