tert-Butanol → HCID 25135993, compound

HRID 1353546Notes

Reaction equation

HRID 1353546 reaction equation
[CH3:1][O:2][C:3](=[O:26])[C@H:4]([NH:15][C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])[CH2:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]=[CH:9]2.C([OH:31])(C)(C)C>[Zn]>[CH3:1][O:2][C:3](=[O:26])[C@H:4]([NH:15][C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])[CH2:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10](=[O:31])[CH2:9]2

Participants

4

Reactant 2

HCID 6386tert-ButanolHCID 25136283HCID 25136283, compound

Product 1

HCID 25135993HCID 25135993, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 23994ZincCatalyst

Procedure

PyHBr3 (1.28 g, 4.02 mmol) was added in small portions over 30 min to a solution of (R)-2-benzyloxycarbonylamino-3-(1H-indol-5-yl)-propionic acid methyl ester (0.47 g, 1.34 mmol) in t-butanol (10 mL) while the reaction temperature was maintained between 25–30° C. The resulting mixture was stirred at room temperature for 3.5 h. The solvent was removed in vacuo, and the residue was extracted with ethyl acetate (2×). The combined organic phases were washed with brine and dried over sodium sulfate. After filtration, solvents were removed and the residue was azeotropically dried with anhydrous ethanol. The residue was dissolved in glacial acetic acid (10 mL) and zinc powder (0.88 g, 13.4 mmol) was added. The mixture was stirred at room temperature overnight. After the acetic acid was removed in vacuo, the residue was purified by flash chromatography on silica gel using ethyl acetate/hexanes [(1:3) first and then (3:2)] as eluent to afford the title compound as a white solid (41% for 2 steps). 1H-NMR (CDCl3, 500 MHz) δ 8.03 (s, 1H), 7.36–7.31 (m, 5H), 6.94 (s, 1H), 6.91 (d, J=8.0 Hz, 1H), 6.73 (d, J=7.5 Hz, 1H), 5.26 (d, J=8.0 Hz, 1H), 5.11 (d, J=12.0 Hz, 1H), 5.05 (d, j=12.5 Hz, 1H), 4.61 (dd, J=13.5, 6.0 hz, 1H), 3.72 (s, 3H), 3.45 (s, 2H), 3.10 (dd, J=14.0, 5.5 Hz, 1H), 3.00 (dd, J=14.0, 6.0 Hz, 1H). 13CNMR (CDCl3, 125 MHz) δ 177.7, 172.2, 155.7, 141.7, 136.3, 129.8, 128.9, 128.6, 128.3, 128.2, 125.8, 125.6, 109.8, 67.1, 55.1, 52.5, 38.0, 36. Mass spec. 369.20 (MH)+.

Workup

  1. temperaturewas maintained between 25–30° C
  2. customThe solvent was removed in vacuo
  3. extractionthe residue was extracted with ethyl acetate (2×)
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationAfter filtration, solvents
  7. customwere removed
  8. dry with materialthe residue was azeotropically dried with anhydrous ethanol
  9. dissolutionThe residue was dissolved in glacial acetic acid (10 mL)
  10. stirringThe mixture was stirred at room temperature overnight
  11. customAfter the acetic acid was removed in vacuo
  12. customthe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-2f33291f8bc24c2d955425865667bd31
Source dataset
uspto-grants-2007_05
Patent number
US07220862B2

Reaction notes

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