Tetrahydrofuran → HCID 60206860, compound

HRID 1985074Notes

Reaction equation

HRID 1985074 reaction equation
[ClH:1].[OH:2][C:3]1[CH:4]=[C:5]([CH:31]=[C:32]([F:34])[CH:33]=1)[CH2:6][C@H:7]([NH:27][C:28](=[O:30])[CH3:29])[C@H:8]([OH:26])[CH2:9][NH:10][C:11]1([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]([CH3:25])[CH3:24])[CH:18]=2)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.Br[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41].CC(C)([O-])C.[K+].C1COCC1.OP([O-])(O)=O.[K+]>CC(C)=O.C(OCC)(=O)C>[ClH:1].[ClH:1].[CH2:36]([O:2][C:3]1[CH:4]=[C:5]([CH:31]=[C:32]([F:34])[CH:33]=1)[CH2:6][C@H:7]([NH:27][C:28](=[O:30])[CH3:29])[C@H:8]([OH:26])[CH2:9][NH:10][C:11]1([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]([CH3:25])[CH3:24])[CH:18]=2)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)[CH2:37][CH2:38][CH2:39][CH2:40][CH3:41]

Participants

9

Reactant 5

HCID 8028TetrahydrofuranHCID 81011-BromohexaneHCID 516951Monobasic potassium phosphateHCID 23665647Potassium tert-butoxideHCID 60206862HCID 60206862, compound

Product 2

HCID 313Hydrochloric AcidHCID 60206860HCID 60206860, compoundYield 125%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 0.40 mmol of hydrochloride 11 in 3 mL of acetone is added 0.29 mL (2.1 mmol) of 1-bromohexane. The mixture is heated to reflux, and 0.6 mL of a 1 M solution of potassium t-butoxide in THF (0.6 mmol) is added. After 1.2 h the mixture is cooled and aqueous 1 N KH2PO4 and ethyl acetate are added. The organic phase is washed twice with 1 N NaHCO3 and once with brine, dried over Na2SO4, and concentrated. Chromatography over silica gel, eluting with 7%-9& methanol (containing 1% of NH4OH) in CH2Cl2, affords a colorless oil. Treatment with ethereal HCl produces 147 mg (0.25 mmol, 64%) of hydrochloride 12 as a white solid: 1H NMR (CDCl3+CD3OD drop) δ 7.45 (s, 1 H), 7.37 (m, 2 H), 7.27 (m, 1 H), 6.50 (s, 1 H), 6.43 (m, 2 H), 3.98 (m, 1 H), 3.88 (m +t, J=6.5 Hz, 3 H), 2.93 (m, 2 H), 2.63 (m, 4 H), 2.38 (m, 1 H), 2.09 (m, 2 H), 1.89 (s, 3 H), 1.75 (m, 4 H), 1.59 (m, 1 H), 1.43-1.32 (m, 10 H), 1.27 (d, J=7 Hz, 6 H), 0.90 (t, J=7 Hz, 3 H); MS (CI) m/z 541.5 (MH+).

Workup

  1. temperatureThe mixture is heated
  2. temperatureto reflux
  3. temperatureAfter 1.2 h the mixture is cooled
  4. washThe organic phase is washed twice with 1 N NaHCO3 and once with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. washChromatography over silica gel, eluting with 7%-9& methanol (containing 1% of NH4OH) in CH2Cl2
  8. customaffords a colorless oil

Sources & evidence

ORD record
ord-5c03c104414f4d5e8131c45708798262
Source dataset
uspto-grants-2009_06
Patent number
US07544717B2

Reaction notes

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