4-Methylmorpholine → Benzyl (4-(hydroxymethyl)bicyclo[2.2.2]octan-1-yl)carbamate

HRID 2109487Notes

Reaction equation

HRID 2109487 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]12[CH2:19][CH2:18][C:15]([C:20](O)=[O:21])([CH2:16][CH2:17]1)[CH2:14][CH2:13]2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.C(Cl)(=O)OCC.[BH4-].[Na+]>O1CCCC1.CO>[CH2:1]([O:8][C:9]([NH:11][C:12]12[CH2:17][CH2:16][C:15]([CH2:20][OH:21])([CH2:18][CH2:19]1)[CH2:14][CH2:13]2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 106622014-(Benzyloxycarbonylamino)bicyclo[2.2.2]octane-1-carboxylic acid

Product 1

HCID 23152946Benzyl (4-(hydroxymethyl)bicyclo[2.2.2]octan-1-yl)carbamateYield 95%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-Benzyloxycarbonylaminobicyclo[2,2,2]octane-1-carboxylic acid (500 mg) was dissolved in tetrahydrofuran (8 mL). While the solution was chilled in a salt/ice bath, N-methylmorpholine (0.18 mL) was added. This was followed by dropwise addition of ethyl chlorocarbonate (0.16 mL) and stirring for 10 minutes. To the reaction mixture, sodium borohydride (187 mg) and then methanol (15 mL) were added and the mixture was stirred below 0° C. for 1 hour. Subsequently, the reaction mixture was concentrated under reduced pressure. To the resulting residue, water was added and the solution was extracted with ethyl acetate. The ethyl acetate layer was then washed sequentially with 1 mol/L hydrochloric acid and water, was dried over anhydrous sodium sulfate, and was concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluant: hexane: ethyl acetate=1:1) to obtain 4-benzyloxycarbonylamino-1-hydroxymethylbicyclo[2,2,2]octane (453 mg).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred below 0° C. for 1 hour
  3. concentrationSubsequently, the reaction mixture was concentrated under reduced pressure
  4. additionTo the resulting residue, water was added
  5. extractionthe solution was extracted with ethyl acetate
  6. washThe ethyl acetate layer was then washed sequentially with 1 mol/L hydrochloric acid and water
  7. dry with materialwas dried over anhydrous sodium sulfate
  8. concentrationwas concentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography (eluant: hexane: ethyl acetate=1:1)

Sources & evidence

ORD record
ord-e8e2d802c6724d40a508034e0e3e88b2
Source dataset
uspto-grants-2009_04
Patent number
US07514571B2

Reaction notes

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