Formaldehyde → HCID 118021888, compound

HRID 1498867Notes

Reaction equation

HRID 1498867 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:13]2[CH:14]=[N:15][C:16]([N:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]3)=[N:17][CH:18]=2)[C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=1.N#N.[Li]CCCC.[CH2:39]=[O:40]>C1COCC1.CC(=O)OCC>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:13]2[CH:14]=[N:15][C:16]([N:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]3)=[N:17][CH:18]=2)([CH2:39][OH:40])[C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 947NitrogenHCID 118022562HCID 118022562, compoundHCID 178418339Butyllithium

Product 1

HCID 118021888HCID 118021888, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of tert-butyl 4-(5-(1-(4-fluorophenyl)-2-methoxy-2-oxoethyl)pyrimidin-2-yl)piperazine-1-carboxylate (650 mg, 1.5 mmol) in THF (20 mL, dry) was cooled to −78° C. and protected with N2. Another solution of n-BuLi (1.5 M, 3 mL, ˜4.5 mmol) in THF was added to the above cooled solution during 5 min. The reaction mixture was stirred at −78° C. for 1 h, followed by the addition of paraformaldehyde (405 mg, 15.0 mmol) in one portion under −78° C. This solution was stirred at RT overnight. The reaction was quenched by saturated aqueous NH4Cl (50 mL) and water (50 mL), and extracted with EtOAc (50 mL*4). The combined organic layer were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel column eluting with PE:EA (4:1) to obtain the title compound as a yellow thicky oil (300 mg, 44% yield). MS (ES+) C23H29FN4O5 requires: 460. found 461 [M+H]+; purity: 93% (UV214).

Workup

  1. stirringThis solution was stirred at RT overnight
  2. customThe reaction was quenched by saturated aqueous NH4Cl (50 mL) and water (50 mL)
  3. extractionextracted with EtOAc (50 mL*4)
  4. washThe combined organic layer were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column
  9. washeluting with PE

Sources & evidence

ORD record
ord-37a85f05de0d4dd1abc9a7880ea06218
Source dataset
uspto-grants-2015_12
Patent number
US09200002B2

Reaction notes

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