Tetrahydrofuran → HCID 11232950, compound

HRID 494876Notes

Reaction equation

HRID 494876 reaction equation
[CH3:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][C:9]1[O:10][C:11]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=3)[C:21](O)=[O:22])=[CH:14][C:12]=2[CH:13]=1.O1CCCC1>>[CH3:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][C:9]1[O:10][C:11]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[C:20]([CH2:21][OH:22])[CH:24]=[CH:25][CH:26]=3)=[CH:14][C:12]=2[CH:13]=1

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 11163902HCID 11163902, compound

Product 1

HCID 11232950HCID 11232950, compoundYield 13%

Conditions

Temperature
60 °C

Procedure

The product from Example 144 (167 mg, 0.48 mmol) was dissolved into 1 M BH3 in tetrahydrofuran (2 mL, 2 mmol), stirred at room temperature overnight, quenched with 0.5 M aqueous dipotassium hydrogen phosphate, and diluted with EtOAc. The organic phase was separated and washed consecutively with 0.5 M aqueous dipotassium hydrogen phosphate and brine, dried (Na2SO4), concentrated, and chromatographed through a short column of silica with a gradient of 0 to 5% MeOH/CH2Cl2, and through a second short column of silica with a gradient of 0 to 5% MeCN/CH2Cl2, collecting and concentrating the material with a mass ion corresponding to a borane complex. This residue was dissolved in methanol (1.5 mL), treated with 0.1 M aqueous hydrochloric acid (0.3 mL), heated at 60° C. for three hours, treated with more 0.1 M aqueous hydrochloric acid (0.1 mL), heated at 60° C. for one hour, concentrated, and chromatographed through a short column of silica with a gradient of 2 to 10% 2 M NH3 in MeOH/CH2Cl2 to provide the title compound as a white powder (13% yield). MS (ESI APCI) m/z 336 (M+H)+; 1HNMR (300 MHz, CD3OD) δ 1.18 (s, 3H), 1.38-1.53 (m, 1H), 1.73-1.87 (m, 2H), 1.94-2.08 (m, 1H), 2.24-2.36 (m, 1H), 2.41-2.60 (m, 2H), 2.94-3.14 (m, 2H), 3.19-3.34 (m, 2H), 4.68 (s, 2H), 6.60 (s, 1H), 7.28-7.34 (m, 1H), 7.40 (dd, 1H), 7.46-7.49 (m, 2H), 7.52 (ddd, 1H), 7.62 (s, 1H), 7.73 (dd, 1H).

Workup

  1. customquenched with 0.5 M aqueous dipotassium hydrogen phosphate
  2. additiondiluted with EtOAc
  3. customThe organic phase was separated
  4. washwashed consecutively with 0.5 M aqueous dipotassium hydrogen phosphate and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customchromatographed through a short column of silica with a gradient of 0 to 5% MeOH/CH2Cl2
  8. customthrough a second short column of silica with a gradient of 0 to 5% MeCN/CH2Cl2, collecting
  9. concentrationconcentrating the material with a mass ion corresponding to a borane complex
  10. dissolutionThis residue was dissolved in methanol (1.5 mL)
  11. additiontreated with 0.1 M aqueous hydrochloric acid (0.3 mL)
  12. additiontreated with more 0.1 M aqueous hydrochloric acid (0.1 mL)
  13. temperatureheated at 60° C. for one hour
  14. concentrationconcentrated
  15. customchromatographed through a short column of silica with a gradient of 2 to 10% 2 M NH3 in MeOH/CH2Cl2

Sources & evidence

ORD record
ord-756762eca4484c09b46d28ce352d3887
Source dataset
uspto-grants-2009_05
Patent number
US07538138B2

Reaction notes

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