Formaldehyde → HCID 178452234, compound

HRID 2206321Notes

Reaction equation

HRID 2206321 reaction equation
[OH:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH:5]=[CH:4][CH:3]=1.[Mg+2].[Cl-].[Cl-].C(N(CC)CC)C.[CH2:31]=[O:32]>CC#N.CCOC(C)=O>[CH:31]([C:3]1[CH:4]=[CH:5][C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:7][C:2]=1[OH:1])=[O:32]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 8471TriethylamineHCID 5360315Magnesium ChlorideHCID 178452235HCID 178452235, compound

Product 1

HCID 178452234HCID 178452234, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of t-butyl 4-(6-hydroxypyridin-2-yl)piperazine-1-carboxylate (8.4 g, 30 mmol) and MgCl2 (5.8 g, 60 mmol) in CH3CN (100 mL) was added triethylamine (25.2 mL, 150 mmol). After the mixture was stirred for 10 minutes at ambient temperature, paraformaldehyde (9.0 g, 300 mmol) was added to the mixture. The mixture was stirred for 18 hours at 60° C., and then cooled to room temperature. The mixture was then diluted with EtOAc (500 mL) and washed with 1 M Rochelle salt solution (200 mL) and saturated NH4Cl solution (200 mL). The organic layer was concentrated under reduced pressure and purified by column chromatography (30%-50% EtOAc/hexanes) to yield 3.6 g (39%) of t-butyl 4-(5-formyl-6-hydroxypyridin-2-yl)piperazine-1-carboxylate as white solid. MS m/z 308.2 [M+H]+; 1H NMR (500 MHz, CDCl3) δ (ppm) 12.35 (1H, br), 9.55 (1H, s), 7.66 (1H, d, J=8.51 Hz), 6.26 (1H, d, J=8.83 Hz), 3.79 (4H, m), 3.56 (4H, m), 1.51 (9H, s).

Workup

  1. stirringThe mixture was stirred for 18 hours at 60° C.
  2. temperaturecooled to room temperature
  3. washwashed with 1 M Rochelle salt solution (200 mL) and saturated NH4Cl solution (200 mL)
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. custompurified by column chromatography (30%-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-836eb5bbcb1f476f8f03705b985bb1a8
Source dataset
uspto-grants-2016_06
Patent number
US09371336B2

Reaction notes

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