Sodium Hydroxide → 1-Morpholino-2-(1-(trityloxy)but-3-en-2-yloxy)ethanone

HRID 707712Notes

Reaction equation

HRID 707712 reaction equation
[C:1]([O:20][CH2:21][CH:22]([OH:25])[CH:23]=[CH2:24])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:27][C:28]([N:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1)=[O:29].[OH-].[Na+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[O:33]1[CH2:34][CH2:35][N:30]([C:28](=[O:29])[CH2:27][O:25][CH:22]([CH:23]=[CH2:24])[CH2:21][O:20][C:1]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:31][CH2:32]1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 74040Morpholine, 4-(chloroacetyl)-HCID 132073271-(Triphenylmethoxy)but-3-en-2-ol

Product 1

HCID 704971151-Morpholino-2-(1-(trityloxy)but-3-en-2-yloxy)ethanoneYield 98.7%

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
2.5 °C

Procedure

To a reactor with 1-(trityloxy)but-3-en-2-ol (41.6 g, 0.111 mol, 1.0 equiv.) was charged toluene (146 mL). The resulting solution was cooled to 0-5° C. and tetra-n-butylammonium hydrogen sulfate (7.52 g, 0.0222 mol, 0.20 equiv.) was charged. 4-(Chloroacetyl)morpholine (18.1 g, 0.111 mol, 1.00 equiv.) was added at 0-5° C. Sodium hydroxide (50% wt. in water; 88.6 g, 1.10 mol, 10 equiv.) was cooled to 15° C. and charged to the reaction mixture with T<10° C. The reaction mixture was stirred for 1 hr at T<15° C. and monitored for consumption of 1-(trityloxy)but-3-en-2-ol (target>99%). To the reaction mixture was charged 2-methoxy-2-methylpropane (146 mL) and water (146 mL) with T<20° C. The organics were washed with 18% aq. NaCl (73 mL) and sat. aq NH4Cl (21 mL). The organics were filtered over Celite (10.4 g) to remove particulates and rinsed with 2-methoxy-2-methylpropane (83 mL). The solvents were evaporated under vacuum T<30° C. to afford a white solid on standing (55.0 g, 98.7% yield accounting for residual solvents). 1H NMR (500 MHz, CDCl3) δ ppm 7.46-7.41 (m, 6H), 7.32-7.25 (m, 6H), 7.25-7.18 (m, 3H), 5.79-5.68 (m, 1H), 5.28 (d, J=17.0 Hz, 1H), 5.26 (d, J=10.1 Hz, 1H), 4.20 (d, J=12.7 Hz, 1H), 4.10 (d, J=12.7 Hz, 1H), 3.97-3.88 (m, 1H), 3.69-3.47 (m, 8H), 3.25 (dd, J=9.9, 6.5 Hz, 1H), 3.17 (dd, J=9.9, 4.3 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ ppm 167.84, 143.84, 134.84, 128.67, 127.78, 127.04, 119.06, 86.73, 81.07, 68.78, 66.78, 66.34, 45.94, 42.16.

Workup

  1. additioncharged to the reaction mixture with T<10° C
  2. custommonitored for consumption of 1-(trityloxy)but-3-en-2-ol (target>99%)
  3. additionTo the reaction mixture was charged 2-methoxy-2-methylpropane (146 mL) and water (146 mL) with T<20° C
  4. washThe organics were washed with 18% aq. NaCl (73 mL) and sat. aq NH4Cl (21 mL)
  5. filtrationThe organics were filtered over Celite (10.4 g)
  6. customto remove particulates
  7. washrinsed with 2-methoxy-2-methylpropane (83 mL)
  8. customThe solvents were evaporated under vacuum T<30° C.
  9. customto afford a white solid

Sources & evidence

ORD record
ord-482e3b7d301142baaea4c35c9c9ad308
Source dataset
uspto-grants-2015_11
Patent number
US09175013B2

Reaction notes

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