Water → HCID 59837355, compound

HRID 273053Notes

Reaction equation

HRID 273053 reaction equation
[N:1]1([C:7]([C:9]2([C:15]3[CH:30]=[CH:29][C:18]([O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)=[CH:17][CH:16]=3)[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=O)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[H-].[H-].[H-].[H-].[Li+].[Al+3].O.[OH-].[Na+]>C1COCC1>[NH3:1].[N:1]1([CH2:7][C:9]2([C:15]3[CH:30]=[CH:29][C:18]([O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)=[CH:17][CH:16]=3)[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 59837372HCID 59837372, compound

Product 2

HCID 222AmmoniaHCID 59837355HCID 59837355, compoundYield 162.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 4-(3-{4-[4-(morpholin-4-ylcarbonyl)tetrahydro-2H-pyran-4-yl]phenoxy}propyl)morpholine (160 mg, 0.38 mmol) in THF (4 mL) at 0° C. was added dropwise a solution of LiAlH4 (1.0M solution in Et2O, 1.15 mL, 1.15 mmol). The reaction mixture was stirred at 0° C. for 20 mins then heated at reflux for 1.5 hours. The reaction was then cooled to 0° C., water (0.10 ml) was added dropwise followed by sodium hydroxide (2.0M, 0.10 ml) and water (0.30 ml). The mixture was filtered through a short pad of celite, eluting with 1% methanol in dichloromethane (15 ml) and the organic washings concentrated in vacuo. The crude compound was purified by column chromatography on silica gel, eluting with dichloromethane:methanol:ammonia, 97:3:0.3 to 92:8:0.8, to give the title compound as a clear oil (125 mg, 81%). 1H NMR (400 MHz, CDCl3) δ 1.83 (m, 2H), 1.95 (m, 2H), 2.07-2.16 (m, 6H), 2.40 (s, 2H), 2.43-2.50 (m, 4H), 2.52 (t, 2H), 3.51 (m, 6H), 3.76 (m, 6H), 4.01 (t, 2H), 6.82 (d, 2H), 7.21 (d, 2H). HRMS ESI+ m/z 405.2742 [MH]+.

Workup

  1. temperaturethen heated
  2. temperatureat reflux for 1.5 hours
  3. temperatureThe reaction was then cooled to 0° C.
  4. filtrationThe mixture was filtered through a short pad of celite
  5. washeluting with 1% methanol in dichloromethane (15 ml)
  6. concentrationthe organic washings concentrated in vacuo
  7. customThe crude compound was purified by column chromatography on silica gel
  8. washeluting with dichloromethane

Sources & evidence

ORD record
ord-f451fe62fc0149c8ad98f339be9792cb
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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