Triethylamine → HCID 178453607, compound

HRID 1984864Notes

Reaction equation

HRID 1984864 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C@H:10]1[CH2:15][CH2:14][C@H:13]([C:16](O)=[O:17])[CH2:12][CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.ClC(OCC)=O.OS([O-])(=O)=O.[K+].[BH4-].[Na+]>C(Cl)Cl.C1COCC1.CO>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][C@H:10]1[CH2:11][CH2:12][C@H:13]([CH2:16][OH:17])[CH2:14][CH2:15]1)([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 516920Potassium bisulfate2×HCID 4311764Sodium borohydrideHCID 178453624HCID 178453624, compound

Product 1

HCID 178453607HCID 178453607, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-65 °C

Procedure

A suspension of trans-4-(tert-butoxycarbonylamino-methyl)-cyclohexane-carboxylic acid (155 g, 603 mmol) in CH2Cl2 (1.35 L) was cooled at −65° C. and triethylamine (126 mL, 904 mmol) and a solution of ethyl chloroformate (58 mL, 751 mmol) in CH2Cl2 (200 mL) were added below −60° C. The reaction mixture was stirred at 0° C. for 50 min. The mixture was acidified with saturated aqueous KHSO4 (pH=3), and the aqueous layer was extracted with CHCl3 (three times). The combined organic layer was washed with saturated aqueous Na2CO3 and brine, dried over MgSO4, filtered, and concentrated to give a colorless oil. A solution of the above oil in THF (1.5 L) was cooled at −65° C. and NaBH4 (26.6 g, 703 mmol) and MeOH (45 mL) were added. The mixture was stirred at −40° C. for 25 min, and stirred at 4° C. for 3 hr. The mixture was acidified with saturated aqueous KHSO4 (pH=3), and the aqueous layer was extracted with EtOAc (three times). The combined organic layer was washed with saturated aqueous Na2CO3 and brine, dried over MgSO4, filtered, and concentrated, and purified by flash chromatography (silica gel, 17% MeOH in CHCl3) to give trans-(4-hydroxymethyl-cyclohexylmethyl)-carbamic acid tert-butyl ester (123 g, 84%) as a white solid.

Workup

  1. extractionthe aqueous layer was extracted with CHCl3 (three times)
  2. washThe combined organic layer was washed with saturated aqueous Na2CO3 and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a colorless oil
  7. stirringThe mixture was stirred at −40° C. for 25 min
  8. stirringstirred at 4° C. for 3 hr
  9. extractionthe aqueous layer was extracted with EtOAc (three times)
  10. washThe combined organic layer was washed with saturated aqueous Na2CO3 and brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. custompurified by flash chromatography (silica gel, 17% MeOH in CHCl3)

Sources & evidence

ORD record
ord-045d39f5e5954b03bc7a9e66ad27e97f
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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