tert-Butanol → HCID 60167284, compound

HRID 2281865Notes

Reaction equation

HRID 2281865 reaction equation
[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[Br:19])[CH:12]=[C:11](C(O)=O)[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC[N:25]([CH2:28]C)CC.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:37])C=CC=CC=1.[CH3:47][C:48]([OH:51])([CH3:50])[CH3:49]>>[C:48]([O:51][C:28](=[O:37])[NH:25][C:11]1[CH:10]=[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[Br:19])[CH:12]=1)([CH3:50])([CH3:49])[CH3:47]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 60167283HCID 60167283, compound

Product 1

HCID 60167284HCID 60167284, compoundYield 89%

Conditions

Temperature
85 °C

Procedure

Carboxylic acid 9 (950 mg, 2.66 mmol) was dissolved in freshly distilled t-BuOH (0.01 M) over 4 Å molecular sieves. Et3N (467 μL, 3.35 mmol) and diphenylphosphoryl azide (602 μL, 2.79 mmol) were added. The reaction mixture was warmed to 85° C. under Ar and stirred for 14 h. Upon completion, the mixture was filtered through cotton to remove the molecular sieves and concentrated under reduced pressure. The residue was diluted with 10% aqueous HCl and extracted with EtOAc (3×). The organic extracts were combined and washed with H2O (2×) and saturated aqueous NaCl. The organic phase was dried over Na2SO4, and concentrated under reduced pressure. Flash chromatography (SiO2, 5×12 cm, 5% EtOAc/hexanes elution) provided 10 (1.02 g, 89%) as a tan solid. 1H NMR (CDCl3, 600 MHz) δ 7.62 (m, 2H), 7.58 (d, J=7.8 Hz, 2H), 7.49 (s, 1H), 7.39 (t, J=7.2 Hz, 2H), 7.33 (t, J=6.0 Hz, 1H), 7.16 (t, J=7.8 Hz, 1H), 7.03 (s, 1H), 6.58 (s, 1H), 5.22 (s, 2H), 1.54 (s, 9H). 13C NMR (CDCl3, 150 MHz) δ 155.2, 152.5, 137.6, 136.4, 136.3, 131.3, 130.0, 128.4, 127.9, 127.3, 126.9, 120.4, 120.2, 120.1, 116.6, 107.8, 101.8, 71.4, 28.3. IR (film) νmax 3325, 2977, 1702, 1156 cm−1. ESI-TOF HRMS m/z 428.0856 (M+H+, C22H22BrNO3 requires 428.0856).

Workup

  1. filtrationUpon completion, the mixture was filtered through cotton
  2. customto remove the molecular sieves
  3. concentrationconcentrated under reduced pressure
  4. additionThe residue was diluted with 10% aqueous HCl
  5. extractionextracted with EtOAc (3×)
  6. washwashed with H2O (2×) and saturated aqueous NaCl
  7. dry with materialThe organic phase was dried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. washFlash chromatography (SiO2, 5×12 cm, 5% EtOAc/hexanes elution)

Sources & evidence

ORD record
ord-526172d4f8564585b7380db6118e8fd8
Source dataset
uspto-grants-2015_09
Patent number
US09139596B2

Reaction notes

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