3-Morpholinone → HCID 59167001, compound

HRID 1443075Notes

Reaction equation

HRID 1443075 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][C:2]1=O.Br[C:9]1(O)[CH:14]=[CH:13][CH:12]=[CH:11][NH:10]1.COCCO[AlH2-]O[CH2:23][CH2:24][O:25]C.[Na+]>C1(C)C=CC=CC=1>[C:23]1([C@H:24]([O:25][C:14]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[C@H:3]2[O:4][CH2:5][CH2:6][NH:1][CH2:2]2)[CH:9]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 669533-Morpholinone2×HCID 16684438Red-AlHCID 22000233HCID 22000233, compound

Product 1

HCID 59167001HCID 59167001, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

(S)-2-[(S)-Phenyl-(pyridin-3-yloxy)-methyl]-morpholine was synthesized from the corresponding amide (6-[Phenyl-(pyridin-3-yloxy)-methyl]-morpholin-3-one) (see Scheme G, compound 8) using the following procedure: A solution of compound 1 (0.30 g, 0.85 mmol) in anhydrous toluene (3.0 mL) was placed under a nitrogen atmosphere, cooled to 0° C. and a commercial solution of Red-Al (65 wt % in toluene, 1.0 mL, 3.3 mmol) was added dropwise via syringe. The reaction mixture was warmed to room temperature over 4 h. TLC analysis showed no starting material remaining. The reaction mixture was again cooled to 0° C. and quenched by the dropwise addition of 2N sodium hydroxide. The reaction mixture was diluted with toluene, the aqueous phase separated and further extracted with toluene. The combined organic extracts were dried over sodium sulphate, filtered, and solvent was removed under reduced pressure to give 0.30 g of light brown oil. Two chromatographies of the reaction product on silica gel (eluent—3:1 ethyl acetate/methanol the second) gave 0.080 g (35%) of the desired product. 1H NMR (400 MHz, CDCl3) δ 8.32 (m, 1H), 8.12 (m, 1H), 7.24 (m, 5H), 7.10 (m, 2H), 5.10 (d, 1H), 3.96 (m, 2H), 3.68 (m, 1H), 2.84 (m, 2H), 2.66 (m, 2H), 1.84 (br s, 1H). (MS) m/z 271.05 [C16H18N2O2+H+]; CHN—C16H18N2O2 Calc'd: C, 71.09%; H, 6.71%; N, 10.36%. Found: C, 70.49%; H, 6.70%; N, 9.83%.

Workup

  1. temperatureThe reaction mixture was warmed to room temperature over 4 h
  2. temperatureThe reaction mixture was again cooled to 0° C.
  3. customquenched by the dropwise addition of 2N sodium hydroxide
  4. additionThe reaction mixture was diluted with toluene
  5. customthe aqueous phase separated
  6. extractionfurther extracted with toluene
  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-6d4981cfed9548cb8d65402738ded529
Source dataset
uspto-grants-2010_02
Patent number
US07659394B2

Reaction notes

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