Formaldehyde → HCID 71112454, compound

HRID 1472750Notes

Reaction equation

HRID 1472750 reaction equation
[C:1]1([CH:7]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:8]([O:10][CH2:11][CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH2:41]=[O:42]>C1COCC1>[OH:42][CH2:41][C:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)([C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[C:8]([O:10][CH2:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1)=[O:9]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 2733832Lithium HexamethyldisilazideHCID 86676457HCID 86676457, compound2×

Product 1

HCID 71112454HCID 71112454, compoundYield 23.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl 4-((2,2-diphenylacetyloxy)methyl)piperidine-1-carboxylate (prepared as in Preparation intermediate 12 with 2,2-diphenylacetic acid replacing cyclohexylmandelic acid) (0.40 g, 0.98 mmol) in THF (5 mL) was treated with lithium hexamethyldisilazide (1.17 mL, 1.17 mmol, 1.0 M solution in THF) followed by formaldehyde (0.20 g, 50% w/w). The reaction mixture was stirred at RT for 16 hours then quenched with saturated aqueous ammonium chloride solution. The aqueous layer was extracted with dichloromethane. The combined organic extracts were dried (magnesium sulfate), filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography eluting with 30-60% ethyl acetate in petroleum ether (40:60) to afford the title compound (0.10 g, 23%).

Workup

  1. customthen quenched with saturated aqueous ammonium chloride solution
  2. extractionThe aqueous layer was extracted with dichloromethane
  3. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by silica gel column chromatography
  7. washeluting with 30-60% ethyl acetate in petroleum ether (40:60)

Sources & evidence

ORD record
ord-410bb90bde454a55b7e1e37614276c7c
Source dataset
uspto-grants-2015_04
Patent number
US09012644B2

Reaction notes

Loading…