Water → HCID 59837531, compound

HRID 273058Notes

Reaction equation

HRID 273058 reaction equation
[N:1]1([CH2:5][CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3([C:21]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)=O)[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:11][CH:10]=2)[CH2:4][CH2:3][CH2:2]1.[H-].[H-].[H-].[H-].[Li+].[Al+3].O.[OH-].[Na+]>C1COCC1>[NH3:1].[N:1]1([CH2:5][CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3([CH2:21][N:23]4[CH2:24][CH2:25][O:26][CH2:27][CH2:28]4)[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:11][CH:10]=2)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 59837468HCID 59837468, compound

Product 2

HCID 222AmmoniaHCID 59837531HCID 59837531, compoundYield 43.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 4-({4-[4-(3-azetidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}carbonyl)morpholine (120 mg, 0.31 mmol) in THF (1 mL) at 0° C. was added dropwise a solution of LiAlH4 (1.0M solution in Et2O, 1.00 mL, 1.00 mmol). The reaction mixture was stirred at 0° C. for 20 mins then heated at reflux for 3 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 94:6:0.6, to give the title compound as a clear oil (25 mg, 22%). 1H NMR (400 MHz, CDCl3) δ 1.78-1.90 (m, 8H), 2.08 (m, 2H), 2.13 (m, 4H), 2.38 (s, 2H), 2.59 (t, 2H), 3.20 (t, 2H), 3.51 (m, 6H), 3.76 (m, 2H), 4.00 (t, 2H), 6.82 (d, 2H), 7.21 (d, 2H). LRMS APCI+ m/z 375 [MH]+.

Workup

  1. temperaturethen heated
  2. temperatureat reflux for 3 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-9df7550dca9f484a97782ba1eb3730bb
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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