Toluene → (4-Formyltetrahydropyran-4-yl)carbamic acid tert-butyl ester

HRID 1925628Notes

Reaction equation

HRID 1925628 reaction equation
[C:1]1([CH3:7])[CH:6]=CC=C[CH:2]=1.[H-].C([Al+]CC(C)C)C(C)C.[C:18]([O:22][C:23]([NH:25][C:26]1([C:32]([O:34]C)=[O:33])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].[Cl-].[NH4+]>CO>[CH:32]([C:26]1([NH:25][C:23](=[O:24])[O:22][C:18]([CH3:20])([CH3:19])[CH3:21])[CH2:27][CH2:28][O:29][CH2:30][CH2:31]1)=[O:33].[C:1]([N:25]([C:26]1([CH2:32][OH:34])[CH2:27][CH2:28][O:29][CH2:30][CH2:31]1)[C:23](=[O:24])[O-:22])([CH3:7])([CH3:6])[CH3:2]

Participants

7

Reactant 4

HCID 1140Toluene2×HCID 25517Ammonium ChlorideHCID 21225700DiisobutylaluminumhydrideHCID 21303801tert-Butyl 4-(methoxycarbonyl)-tetrahydro-2H-pyran-4-ylcarbamate

Product 2

HCID 59718793(4-Formyltetrahydropyran-4-yl)carbamic acid tert-butyl esterHCID 86619945N-t-butyl-(4-hydroxymethyl-tetrahydro-pyran-4-yl)-carbamate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The toluene solution of diisobutylaluminum hydride (72.3 mL, 73.0 mmol) was dropped in the dehydrated toluene (50 mL) solution of methyl 4-t-butoxycarbonylamino-tetrahydro-pyran-4-carboxylate (4.74 g, 18.3 mmol) which had been obtained in 1) at −78° C. for 1 hour. After the reaction mixture had been stirred at the same temperature for 20 minutes, saturated aqueous ammonium chloride solution (20 mL) was dropped in 10 minutes and the mixture was stirred at room temperature for 15 minutes. Then, methanol (3 mL) was added and the mixture was further stirred at room temperature for 20 minutes. The precipitated insoluble matter was removed by filtration with Celite, and the filtrate was extracted with ethyl acetate. The organic layer was washed with water and saturated saline in order, and then dried with anhydrous magnesium sulfate. The crude product was refined with silica gel column chromatography (the ethyl acetate-hexane solution of 3:7 to 1:0 in mixing ratio) to give the desired product of colorless oily matter (2.00 g) and N-t-butyl-(4-hydroxymethyl-tetrahydro-pyran-4-yl)-carbamate (1.32 g).

Workup

  1. customhad been obtained in 1) at −78° C. for 1 hour
  2. stirringthe mixture was stirred at room temperature for 15 minutes
  3. stirringthe mixture was further stirred at room temperature for 20 minutes
  4. customThe precipitated insoluble matter was removed by filtration with Celite
  5. extractionthe filtrate was extracted with ethyl acetate
  6. washThe organic layer was washed with water and saturated saline in order
  7. dry with materialdried with anhydrous magnesium sulfate
  8. additionin mixing ratio)

Sources & evidence

ORD record
ord-789fc7dfaf494bc3a7b8ccc9bf82ff25
Source dataset
uspto-grants-2012_05
Patent number
US08178681B2

Reaction notes

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