Trifluoroacetic acid → tert-Butyl 6-bromo-3',6'-dihydro-2,4'-bipyridine-1'(2'H)-carboxylate

HRID 2039721Notes

Reaction equation

HRID 2039721 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](O)([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Br:20])[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O.C(N(CC)CC)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>CO>[Br:20][C:16]1[N:15]=[C:14]([C:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH:10]=2)[CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 86614831tert-Butyl 4-(6-bromopyridin-2-yl)-4-hydroxypiperidine-1-carboxylate

Product 1

HCID 86614830tert-Butyl 6-bromo-3',6'-dihydro-2,4'-bipyridine-1'(2'H)-carboxylateYield 50.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
128 °C

Procedure

As shown in FIG. 7—step ii, compound 1031 (2.0 g) was mixed with TFA (25 mL) in a sealed tube and heated at 128° C. for 2 days. Removal of the TFA gave a residue, which was dissolved in methanol (30 mL) and treated with triethylamine (2 mL) and di-tert-butyl dicarbonate (1.4 mL). After 1 hour, the volatiles were removed in vacuo and water (100 mL) was added. Extraction with dichloromethane (3×), concentration, and purification by chromatography (SiO2, 20% ethyl acetate/hexane) gave 6-bromo-3′,6′-dihydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid, tert-butyl ester (compound 1032) (0.96 g).

Workup

  1. customRemoval of the TFA
  2. customgave a residue, which
  3. customthe volatiles were removed in vacuo and water (100 mL)
  4. additionwas added
  5. extractionExtraction
  6. concentrationwith dichloromethane (3×), concentration, and purification by chromatography (SiO2, 20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-c15d939012d8409bbe3ac184aa8c170a
Source dataset
uspto-grants-2013_11
Patent number
US08580802B2

Reaction notes

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