Acetic Acid → (+/-)Tert-butyl 7-(((6-methylpyridin-2-yl)amino)methyl)-8-azaspiro[4.5]decane-8-carboxylate

HRID 536594Notes

Reaction equation

HRID 536594 reaction equation
[CH:1]([CH:3]1[N:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH2:10][C:5]2([CH2:9][CH2:8][CH2:7][CH2:6]2)[CH2:4]1)=O.C(O)(=O)C.[NH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[N:26]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C.C([O-])(O)=O.[Na+]>[CH3:31][C:27]1[N:26]=[C:25]([NH:24][CH2:1][CH:3]2[N:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH2:10][C:5]3([CH2:9][CH2:8][CH2:7][CH2:6]3)[CH2:4]2)[CH:30]=[CH:29][CH:28]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 157652-Amino-6-methylpyridineHCID 5049666Sodium triacetoxyborohydrideHCID 86664866(+/-)Tert-butyl 7-formyl-8-azaspiro[4.5]decane-8-carboxylate2×

Product 1

HCID 66848215(+/-)Tert-butyl 7-(((6-methylpyridin-2-yl)amino)methyl)-8-azaspiro[4.5]decane-8-carboxylateYield 48.3%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

(±)tert-butyl 7-formyl-8-azaspiro[4.5]decane-8-carboxylate (Intermediate 72, 2 g, 7.48 mmol) was dissolved in dichloroethane (25 ml), then acetic acid (5 eq) and 2-amino 6 picoline (810 mg, 7.48 mmol) were added. After 3 hours at room temperature NaBH(OAc)3 (2.53 g, 11.96 mmol) was added and the reaction was maintained under stirring at room temperature for 18 hours. The reaction was poured in aqueous NaHCO3 and extracted with ethylacetate. The organic layers were combined, dried (Na2SO4) and concentrated under vacuum; the crude was then purified by silica gel column chromatography (petroleum ether/ethyl acetate=9/1) to obtain 1.3 g of intermediate as colourless oil.

Workup

  1. temperaturethe reaction was maintained
  2. extractionextracted with ethylacetate
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under vacuum
  5. customthe crude was then purified by silica gel column chromatography (petroleum ether/ethyl acetate=9/1)

Sources & evidence

ORD record
ord-f82197d65d3f4404bebfa01b26061eea
Source dataset
uspto-grants-2014_10
Patent number
US08859608B2

Reaction notes

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