Formaldehyde → HCID 57849006, compound

HRID 736454Notes

Reaction equation

HRID 736454 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[C:16]1[CH2:20][C:19]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([CH2:21][CH2:22][CH2:23][O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)[N:18]([C:37](=[O:42])[C:38]([F:41])([F:40])[F:39])[N:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:53]=[O:54]>C1COCC1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[C:16]1[CH:20]([CH2:53][OH:54])[C:19]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)([CH2:21][CH2:22][CH2:23][O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)[N:18]([C:37](=[O:42])[C:38]([F:40])([F:39])[F:41])[N:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 712Formaldehyde2×HCID 2724254Sodium bis(trimethylsilyl)amideHCID 86621810HCID 86621810, compound

Product 1

HCID 57849006HCID 57849006, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

To a solution of 13.0 g (22.2 mmol) 3-5 in 150 ml of THF at −78° C. was added dropwise a solution of 22.2 ml (44.4 mmol) 2 M NaHMDS in THF. After the addition was complete, the solution was warmed to −40° C. and stirred for 45 min. In a separate flask, 40 g of paraformaldehyde was mixed with 100 ml of mineral oil and heated at 140° C. A stream of argon was passed over the paraformaldehyde/mineral oil mixture and the resulting formaldehyde gas was bubbled into the above solution of C-5 still at −40° C. for 15 minutes. The cold solution was quenched with 100 ml of saturated aqueous NH4Cl and allowed to warm to room temperature. The mixture was dumped into a separatory funnel with EtOAc and the layers were separated. The aqueous was extracted with EtOAc, the combined organics were washed with brine, dried over MgSO4, and concentrated. The residue was purified by silica gel chromatography with EtOAc/hexanes to provide 3-6 as an amber gum. Data for 3-6: LC-MS: rt=3.1 min, m/z=531 (M−THP+1).

Workup

  1. additionAfter the addition
  2. temperatureheated at 140° C
  3. customthe resulting formaldehyde gas was bubbled into the above solution of C-5 still at −40° C. for 15 minutes
  4. customThe cold solution was quenched with 100 ml of saturated aqueous NH4Cl
  5. temperatureto warm to room temperature
  6. customThe mixture was dumped into a separatory funnel with EtOAc
  7. customthe layers were separated
  8. extractionThe aqueous was extracted with EtOAc
  9. washthe combined organics were washed with brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated
  12. customThe residue was purified by silica gel chromatography with EtOAc/hexanes

Sources & evidence

ORD record
ord-a8c144a033094f2ab5b209a257cf9e88
Source dataset
uspto-grants-2009_09
Patent number
US07595337B2

Reaction notes

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