Hydrochloric Acid → tert-Butyl (4-hydroxy-2-methylbutan-2-yl)carbamate

HRID 582398Notes

Reaction equation

HRID 582398 reaction equation
ClC(OCC)=O.[C:7]([O:11][C:12]([NH:14][C:15]([CH3:21])([CH3:20])[CH2:16][C:17](O)=[O:18])=[O:13])([CH3:10])([CH3:9])[CH3:8].C(N(CC)CC)C.[Li].Cl>O1CCCC1.CO>[C:7]([O:11][C:12](=[O:13])[NH:14][C:15]([CH3:21])([CH3:20])[CH2:16][CH2:17][OH:18])([CH3:10])([CH3:8])[CH3:9]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 3028194LithiumHCID 103760463-((tert-Butoxycarbonyl)amino)-3-methylbutanoic acid

Product 1

HCID 15473340tert-Butyl (4-hydroxy-2-methylbutan-2-yl)carbamateYield 78.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

##STR104## At 0° C., ethyl chloroformate (1.101/2, 11.5 mmol) was given dropwise to a solution of 3-tert-butoxycarbonylamino-3-methylbutanoic acid (2.50 g, 11.5 mmol) and triethylamine (1.92 mL, 13.8 mmol) in tetrahydrofuran (10 mL). The solution was stirred for 40 min at 0° C. The formed precipitate was filtered off and washed with tetrahydrofuran (20 mL). The liquid was immediately cooled to 0° C. A 2M solution of lithium boronhydride in tetrahydrofuran (14.4 mL, 28.8 mmol) was added dropwise. The solution was stirred at 0° C. for 2 h, and then warmed to room temperature over a period of 4 h. It was cooled to 0° C. Methanol (5 mL) was added carefully. 1N Hydrochloric acid (100 mL) was added. The solution was extracted with ethyl acetate (2×100 mL, 3×50 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was chromatographed on silica (110 g) with ethyl acetate/heptane 1:2 to give 1.84 g of 3-hydroxy-1,1-dimethylpropylcarbamic acid tert-butyl ester.

Workup

  1. custom##STR104## At 0° C.
  2. filtrationThe formed precipitate was filtered off
  3. washwashed with tetrahydrofuran (20 mL)
  4. temperatureThe liquid was immediately cooled to 0° C
  5. stirringThe solution was stirred at 0° C. for 2 h
  6. temperaturewarmed to room temperature over a period of 4 h
  7. temperatureIt was cooled to 0° C
  8. extractionThe solution was extracted with ethyl acetate (2×100 mL, 3×50 ml)
  9. washThe combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml)
  10. dry with materialdried over magnesium sulfate
  11. customThe solvent was removed in vacuo
  12. customThe crude product was chromatographed on silica (110 g) with ethyl acetate/heptane 1:2

Sources & evidence

ORD record
ord-c771c5bc95684044b50bce27f57c83c8
Source dataset
uspto-grants-1999_07
Patent number
US05922770

Reaction notes

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