Formaldehyde → HCID 67516965, compound

HRID 2173373Notes

Reaction equation

HRID 2173373 reaction equation
[Br:1][C:2]1[C:3]([CH3:15])=[CH:4][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[N:6][CH:7]=1.C(NC(C)C)(C)C.[Li].[CH2:24]=[O:25]>C1COCC1.CCCCCCC.O1CCCC1.C(C1C=CC=CC=1)C.C(=O)(O)[O-].[Na+]>[Br:1][C:2]1[C:3]([CH2:15][CH2:24][OH:25])=[CH:4][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:11])([CH3:12])[CH3:13])=[N:6][CH:7]=1

Participants

7

Reactant 3

HCID 712FormaldehydeHCID 45051747Lithium diisopropylamineHCID 67517361HCID 67517361, compound

Product 1

HCID 67516965HCID 67516965, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolventHCID 22742125Tetrahydrofuran heptane ethylbenzolSolvent

Procedure

A solution of N-(5-bromo-4-methylpyridin-2-yl)-2,2-dimethylpropanamide (30.0 g, 111 mmol) in THF (80 mL) was cooled in an ice bath and treated dropwise with a solution of lithium diisopropylamine in heptane/tetrahydrofuran/ethylbenzene (2.0 M, 138 mL) After stirring 1 h, the solution was treated with paraformaldehyde (24.9 g, 277 mmol) and allowed to warm gradually to room temperature while stirring 12 h. The mixture was diluted with saturated sodium bicarbonate solution and extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. Purification by MPLC (eluent 6-50% ethyl acetate/hexanes) afforded N-[5-bromo-4-(2-hydroxyethyl)pyridin-2-yl]-2,2-dimethylpropanamide. 1H NMR (500 MHz, CDCl3), δ 8.33 (s, 1H), 8.30 (s, 1H), 8.02 (br s, 1H), 3.98 (dd, J=6.5, 6.5 Hz, 2H), 3.04 (dd, J=6.5, 6.5 Hz, 2H), 1.34 (s, 9H); LC/MS (M+1)+=300.87;

Workup

  1. stirringwhile stirring 12 h
  2. extractionextracted with ethyl acetate (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by MPLC (eluent 6-50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f74085ad615d4dc290d023eb650b0102
Source dataset
uspto-grants-2015_06
Patent number
US09056859B2

Reaction notes

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