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

HRID 581196Notes

Reaction equation

HRID 581196 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.[BH4-].[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 4148881Lithium borohydrideHCID 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) (cf. Schoen et al. J. Med. Chem., 1994, vol. 37, p. 897-906, and references cited herein) 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 borohydride 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. and methanol (5 ml) was added. 1N Hydrochloric acid (100 ml) was added and the solution was extracted with ethyl acetate (2×100 ml, 3×50 ml). The combined organic extracts were washed with saturated sodium hydrogencarbonate 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 aceteate/heptane (1:2) to give 1.84 g of 3-hydroxy-1,1dimethylpropylcarbamic acid tert-butyl ester.

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 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 extracts were washed with saturated sodium hydrogencarbonate 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 aceteate/heptane (1:2)

Sources & evidence

ORD record
ord-e57446e6ff5b444d85113a7843335c38
Source dataset
uspto-grants-1999_07
Patent number
US05919777

Reaction notes

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