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

HRID 1601930Notes

Reaction equation

HRID 1601930 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

At 0° C., ethyl chloroformate (1.10 mL, 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. 1H-NMR (CDCl3): d 1.33 (s, 6 H); 1.44 (s, 9 H); 1.88 (t, 2 H); 1.94 (br, 1H); 3.75 (q, 2 H); 4.98 (br, 1 H). ##STR11##

Workup

  1. customAt 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
  7. waitover a period of 4 h
  8. temperatureIt was cooled to 0° C
  9. extractionThe solution was extracted with ethyl acetate (2×100 mL, 3×50 mL)
  10. washThe combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 mL)
  11. dry with materialdried over magnesium sulfate
  12. customThe solvent was removed in vacuo
  13. customThe crude product was chromatographed on silica (110 g) with ethyl acetate/heptane 1:2

Sources & evidence

ORD record
ord-f031a050f61c4d09a815920a85e6d090
Source dataset
uspto-grants-1999_11
Patent number
US05977178

Reaction notes

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