Hydrochloric Acid → HCID 59166871, compound

HRID 1443076Notes

Reaction equation

HRID 1443076 reaction equation
[Br:1][C:2]1(O)[CH:7]=[CH:6][CH:5]=[CH:4][NH:3]1.B.[O:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1.Cl.[OH-:16].[Na+].O1[CH2:22][CH2:21][CH2:20][CH2:19]1>>[Br:1][C:2]1[C:7]([O:16][C@@H:13]([C:12]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:11]=2)[C@H:14]2[O:10][CH2:7][CH2:2][NH:3][CH2:4]2)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 22000233HCID 22000233, compound

Product 1

HCID 59166871HCID 59166871, compound

Procedure

(S)-2-[(S)-(2-Bromo-pyridin-3-yloxy)-phenyl-methyl]-morpholine was synthesized from the corresponding amide (6-[Phenyl-(pyridin-3-yloxy)-methyl]-morpholin-3-one) using the following procedure: To a solution of compound 1 (0.4 g, 1.1 mmol) in anhydrous tetrahydrofuran (10 mL) under a nitrogen atmosphere was added a commercial solution of borane-tetrahydrofuran complex (1.0M in tetrahydrofuran, 3.4 mL, 3.4 mmol) via syringe. The reaction mixture was stirred at room temperature for 20 h. TLC analysis showed no reaction had occurred. A further amount of borane-tetrahydrofuran complex (3.0 mL, 3.0 mmol) was added and the reaction mixture was heated at reflux for 2.5 h. TLC analysis showed no starting material. The reaction mixture was brought to room temperature, treated with 1N HCl, stirred for 30 minutes, basified by the addition of 2N sodium hydroxide and extracted with ethyl acetate. The combined organic extracts were dried over sodium sulphate, filtered, and solvent was removed under reduced pressure. Two chromatographies of the reaction product on silica gel (eluent—3:1 ethyl acetate/methanol for first chromatography, 10:1 dichloromethane/methanol for the second) gave 0.063 g (16%) of the desired product. 1H NMR (400 MHz, CDCl3) δ 7.90 (m, 1H), 7.36 (m, 5H), 7.00 (m, 2H), 5.16 (d, 1H), 3.96 (m, 2H), 3.68 (m, 1H), 2.82 (m, 2H), 2.64 (m, 2H), 1.80 (br s, 1H). (MS) m/z 350.92 [Cl6H17BrN2O2+H+] HPLC—91.49% CHN—C22H21FN2O2 Calc'd: C, 55.03%; H, 4.91%; N, 8.02%. Found: C, 55.01%; H, 4.97%; N, 8.60%.

Workup

  1. additionA further amount of borane-tetrahydrofuran complex (3.0 mL, 3.0 mmol) was added
  2. temperaturethe reaction mixture was heated
  3. temperatureat reflux for 2.5 h
  4. customwas brought to room temperature
  5. stirringstirred for 30 minutes
  6. extractionextracted with ethyl acetate
  7. dry with materialThe combined organic extracts were dried over sodium sulphate
  8. filtrationfiltered
  9. customsolvent was removed under reduced pressure

Sources & evidence

ORD record
ord-84ebfeca1d65465fa0941a24875ee6ad
Source dataset
uspto-grants-2010_02
Patent number
US07659394B2

Reaction notes

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