Benzaldehyde → HCID 68109410, compound

HRID 2179437Notes

Reaction equation

HRID 2179437 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:14][C:13]3[CH2:12][CH2:11][N:10]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:9][C:8]=3[C:6]=2[CH:7]=1.C([Li])CCC.[CH:27](=[O:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[NH4+].[Cl-:36]>C1COCC1>[Cl:36][C:4]1[C:5]2[O:14][C:13]3[CH2:12][CH2:11][N:10]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:9][C:8]=3[C:6]=2[CH:7]=[C:2]([CH:27]([OH:34])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:3]=1

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 25517Ammonium ChlorideHCID 68109313HCID 68109313, compoundHCID 178418339Butyllithium

Product 1

HCID 68109410HCID 68109410, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of the product of Example 29 step B (1.0 g, 2.58 mmol) in dry THF (15 mL) was cooled to −78° C. under a nitrogen atmosphere and n-butyl lithium (1.6 M in hexane, 1.0 mL, 1.54 mmol) was added dropwise over 10 min. The reaction mixture was stirred for 20 min and a solution of benzaldehyde (137 mg, 1.29 mmol) in THF (1 mL) was added over 5 min. The reaction was stirred for 1 h at −78° C., poured into saturated NH4Cl solution and extracted with ethyl acetate. The organic layer was dried over Na2SO4, concentrated in vacuo and the residue purified by flash column chromatography (SiO2, 85:15 hexanes/ethyl acetate) to afford tert-butyl 6-chloro-8-(hydroxy(phenyl)methyl)-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate (0.6 g, 56%) as a white solid: 1H NMR (CDCl3, 300 MHz) δ 7.42-7.26 (m, 7H), 5.91 (d, J=3.3 Hz, 1H), 4.51 (s, 2H), 3.87-3.75 (m, 2H), 2.93-2.83 (m, 2H), 2.28 (d, J=3.3 Hz, 1H), 1.49 (s, 9H).

Workup

  1. stirringThe reaction was stirred for 1 h at −78° C.
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customthe residue purified by flash column chromatography (SiO2, 85:15 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-5ffc66ae9c5743d4955ebd0a07cdd6dd
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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