Water → HCID 178484049, compound

HRID 967122Notes

Reaction equation

HRID 967122 reaction equation
[C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([CH2:15][OH:16])[CH2:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Al+3].[Li+].[H-].[H-].[H-].[C:24](OC(OC(OC(C)(C)C)=O)=O)(C)(C)C.O>O1CCCC1.C(OCC)(=O)C.CO.C(N(CC)CC)C>[C:1]([O:5][C:6](=[O:17])[N:7]([CH2:8][C@H:9]1[CH2:10][CH2:11][C@H:12]([CH2:15][OH:16])[CH2:13][CH2:14]1)[CH3:24])([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 4

HCID 962WaterHCID 90495Di-tert-butyl dicarbonateHCID 21226445Aluminium lithium hydrideHCID 178453607HCID 178453607, compound

Product 1

HCID 178484049HCID 178484049, compoundYield 88.3%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

2.90 g (11.0 mmol) trans-(4-hydroxymethyl-cyclohexylmethyl)-carbamic acid tert-butyl ester [U.S. (2000) U.S. Pat. No. 6,022,969 A] dissolved in 15 ml of tetrahydrofuran were added slowly to a suspension of 0.92 g of lithium aluminium hydride in 10 ml of tetrahydrofuran. The reaction mixture was then stirred at 50° C. for 4 hours, cooled to 0° C., treated with 2 g of ice, stirred at room temperature for 30 min., diluted with ethyl acetate, dried over sodium sulfate, filtered and evaporated. Thus, crude trans-(4-methylaminomethyl-cyclohexyl)-methanol was obtained [MS: 158 (MH+)], which was dissolved in 20 ml of methanol, cooled to −10° C. and treated at once with 2.77 g di-tert-butyl-dicarbonate. Then, the reaction mixture was stirred at −10° C. for 30 min. and at room temperature for 1 hour. Subsequently, 5 ml of water and 5 ml of triethylamine were added and the reaction mixture evaporated under reduced pressure. It was then poured into 100 ml of an ice/water mixture and extracted 3 times with 100 ml of dichloromethane. The combined dichloromethane phases were dried over magnesium sulfate and evaporated under reduced pressure. The residue formed was chromatographed on silica gel with a 1:1 v/v mixture of dichloromethane and ethylacetate as the eluent giving 2.5 g (82%) trans-(4-hydroxymethyl-cyclohexylmethyl)-methyl-carbamic acid tert-butyl ester as colorless viscous oil, MS: 257 (M+).

Workup

  1. temperaturecooled to 0° C.
  2. stirringstirred at room temperature for 30 min.
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThus, crude trans-(4-methylaminomethyl-cyclohexyl)-methanol was obtained [MS: 158 (MH+)], which
  7. temperaturecooled to −10° C.
  8. stirringThen, the reaction mixture was stirred at −10° C. for 30 min. and at room temperature for 1 hour
  9. customthe reaction mixture evaporated under reduced pressure
  10. additionIt was then poured into 100 ml of an ice/water mixture
  11. extractionextracted 3 times with 100 ml of dichloromethane
  12. dry with materialThe combined dichloromethane phases were dried over magnesium sulfate
  13. customevaporated under reduced pressure
  14. customThe residue formed
  15. customwas chromatographed on silica gel with a 1:1 v/v mixture of dichloromethane and ethylacetate as the eluent

Sources & evidence

ORD record
ord-4ab404c008cc47ccba22655ac1363895
Source dataset
uspto-grants-2005_10
Patent number
US06953806B2

Reaction notes

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