Triethylamine → HCID 86714597, compound

HRID 1025938Notes

Reaction equation

HRID 1025938 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]([CH3:21])([CH2:16][C:17]([F:20])([F:19])[F:18])[C:13](O)=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.ClC(OCC)=O.[BH4-].[Na+]>C1COCC1.O>[F:18][C:17]([F:19])([F:20])[CH2:16][C:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([CH3:21])[CH2:13][OH:14]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 86714596HCID 86714596, compound

Product 1

HCID 86714597HCID 86714597, compoundYield 55.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-(benzyloxycarbonylamino)-4,4,4-trifluoro-2-methylbutanoic acid (1.6 g, 5.2 mmol) in THF (17 ml) was cooled to 0° C. and triethylamine (910 ul, 6.5 mmol) was added, then ethyl chloroformate (624 ul, 6.5 mmol) dropwise over 40 min. A solution of sodium borohydride (491 mg, 13 mmol) in H2O (2.6 ml) was added dropwise over 2 h. The reaction was quenched by the addition of 1 M HCl, stirred for 5 min, and then extracted with EtOAc. The organic layer was washed with sat. NaHCO3, sat. NaCl, dried on Na2SO4, and concentrated in vacuo. The residue was purified by flash chromatography (15% to 100% EtOAc in hexanes) to afford the title compound as a clear oil (838 mg). 1H NMR (CDCl3, 400 MHz) δ 1.36 (s, 3H), 2.33-2.45 (m, 1H), 2.93-3.03 (m, 1H), 3.62 (br s, 1H), 3.65-3.76 (m, 2H), 5.07-5.10 (m, 3H), 7.28-7.39 (m, 5H). LRMS (ESI/APCI): 292 [M+H]+.

Workup

  1. customThe reaction was quenched by the addition of 1 M HCl
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with sat. NaHCO3, sat. NaCl
  4. customdried on Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography (15% to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-d3608b483e4c40d887a37f6e33abbf9f
Source dataset
uspto-grants-2014_05
Patent number
US08729112B2

Reaction notes

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