Borane;tetrahydrofuran → HCID 57440699, compound

HRID 2252643Notes

Reaction equation

HRID 2252643 reaction equation
B.O1CCCC1.[CH2:7]([CH:9]1[O:14][CH:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=2)[CH2:12][N:11]([CH2:23][CH2:24][CH3:25])[C:10]1=O)[CH3:8]>C1COCC1>[CH2:7]([CH:9]1[O:14][CH:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=2)[CH2:12][N:11]([CH2:23][CH2:24][CH3:25])[CH2:10]1)[CH3:8]

Participants

4

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 57440698HCID 57440698, compound

Product 1

HCID 57440699HCID 57440699, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

Borane-tetrahydrofuran complex (1 M in THF) (3 mL, 3 mmol) was added dropwise to the product from example 45 (0.33 g, 1.18 mmol) in dry THF (4 mL) under an atmosphere of nitrogen. The reaction mixture was heated at 85° C. for 3 hours then cooled and quenched by the addition of methanol (1 mL). The reaction mixture was then concentrated in vacuo and the residue suspended in 6N HCl (aq) (10 mL) and heated to 60° C. for 1.5 hours. The reaction mixture was cooled and extracted with diethyl ether (2×10 mL). The aqueous layer was rendered basic (pH 9-10) by addition of solid potassium carbonate before re-extracting with dichloromethane (2×15 mL). The dichloromethane extracts were dried over anhydrous magnesium sulphate, filtered and concentrated in vacuo to give the crude products as a clear oil. Purification by column chromatography on silica eluting with ethyl acetate:pentane (1:10) yielded the two title compounds as single diastereomers. Example 46A: clear oil (0.10 g, 0.38 mmol, 32%): 1H NMR (CDCl3, 400 MHz) δ: 1.00 (m 6H), 1.60 (bm, 3H), 1.85 (m, 1H), 2.25 (bt, 2H), 2.35 (s, 1H), 2.45 (m, 1H), 2.60 (m, 1H), 2.65 (m, 1H), 3.70 (s, 1H), 3.80 (s, 3H), 4.80 (s, 1H), 6.80 (d, 1H), 7.00 (m, 2H), 7.25 (m, 1H). LRMS (APCl): m/z 264 (M−H+). Example 46B: clear oil (0.10 g, 0.38 mmol, 32%): 1H NMR (CDCl3, 400 MHz) δ: 0.90 (t, 3H), 1.00 (t, 3H), 1.60 (bm, 4H), 1.80 (bs, 1H), 2.00 (bs, 1H), 2.35 (bs, 2H), 2.85 (bd, 1H), 2.95 (bd, 1H), 3.60 (s, 1H), 3.80 (s, 3H), 4.60 (s, 1H), 6.80 (d, 1H), 6.95 (s, 2H), 7.25 (t, 1H). LRMS (APCl): m/z 264 (MH+).

Workup

  1. temperaturethen cooled
  2. customquenched by the addition of methanol (1 mL)
  3. concentrationThe reaction mixture was then concentrated in vacuo
  4. temperatureheated to 60° C. for 1.5 hours
  5. temperatureThe reaction mixture was cooled
  6. extractionextracted with diethyl ether (2×10 mL)
  7. additionby addition of solid potassium carbonate
  8. extractionbefore re-extracting with dichloromethane (2×15 mL)
  9. dry with materialThe dichloromethane extracts were dried over anhydrous magnesium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto give the crude products as a clear oil
  13. customPurification by column chromatography on silica eluting with ethyl acetate:pentane (1:10)
  14. customyielded the two title compounds as single diastereomers

Sources & evidence

ORD record
ord-5294e33d8ae740dab9f137a4a5434e7c
Source dataset
uspto-grants-2008_01
Patent number
US07323462B2

Reaction notes

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