Formaldehyde → HCID 69586068, compound

HRID 1610997Notes

Reaction equation

HRID 1610997 reaction equation
[CH:1](NC(C)C)([CH3:3])[CH3:2].[CH2:8]([Li])[CH2:9][CH2:10][CH3:11].[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH2:20][O:21][C:22]1[C:27]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[Cl:36])=[CH:26][CH:25]=[CH:24][C:23]=1CC(O)=O.[CH2:41]=[O:42].CC[O:45][C:46]([CH3:48])=[O:47]>C1COCC1.CN1C(=O)N(C)CCC1>[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH2:20][O:21][C:22]1[C:27]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[Cl:36])=[CH:26][CH:25]=[CH:24][C:23]=1[CH2:11][C:10]1[CH:3]=[CH:1][CH:2]=[CH:8][C:9]=1[CH:48]([CH2:41][OH:42])[C:46]([OH:45])=[O:47]

Participants

8

Reactant 5

HCID 712Formaldehyde2×HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 10126984HCID 10126984, compoundHCID 178418339Butyllithium

Product 1

HCID 69586068HCID 69586068, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of diisopropylamine (160 μL, 1.14 mmol) under argon at −5° C. in THF (3 mL) was added n-butyllithium solution (0.43 mL, 2.5 M in hexanes, 1.08 mmol). After 15 min, the reaction mixture was cooled to −78° C. and a solution of Example 5 Part E compound (209 mg, 0.5 mmol) in THF (1 mL) was then added over 2 min. After an additional 15 min, DMPU was added (2 mL) and the solution warmed to 0° C. Formaldehyde gas (by the pyrolysis of paraformaldehyde [300 mg, 10 mmol] at 190° C.) was introduced to the reaction mixture by a gas inlet tube. The reaction mixture was stirred for 1 h, diluted with EtOAc, washed once with 5% potassium hydrogen sulfate, dried (MgSO4) and evaporated. Purification by flash chromatography on silica gel (1:39:360 HOAc/MeOH/CH2Cl2 as elutent) provided the title compound as a white solid, 136 mg (61% yield). LC/MS gave the correct molecular ion [(M+H)+=447] for the desired compound.

Workup

  1. waitAfter an additional 15 min
  2. temperaturethe solution warmed to 0° C
  3. washwashed once with 5% potassium hydrogen sulfate
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customPurification by flash chromatography on silica gel (1:39:360 HOAc/MeOH/CH2Cl2 as elutent)

Sources & evidence

ORD record
ord-fe82d707f1654ee3a7767ba4b8214d14
Source dataset
uspto-grants-2006_01
Patent number
US06984645B2

Reaction notes

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