Water → HCID 11688814, compound

HRID 272953Notes

Reaction equation

HRID 272953 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3([CH2:23][NH:24][C:25](=O)OC(C)(C)C)[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:13][CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3].O.[OH-].[Na+]>C1COCC1.ClCCl.CO>[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3([CH2:23][NH:24][CH3:25])[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)=[CH:13][CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydride2×HCID 86601901HCID 86601901, compound

Product 1

HCID 11688814HCID 11688814, compoundYield 94%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred solution of tert-butyl [4-(4-[(1-isopropylpiperidin-4-yl)oxy]phenyl)tetrahydro-2H-pyran-4-yl]methylcarbamate (532 mg, 1.23 mmol) in THF (3.5 ml) at 0° C. was added dropwise a solution of LiAlH4 (1.0M solution in Et2O, 3.69 ml, 3.69 mmol). Reaction stirred for 60 hours at ambient temperature before a further dropwise addition of LiAlH4 (1.0M solution in Et2O, 0.6 ml, 0.6 mmol). Heated at 40° C. until reaction complete. The reaction was then cooled to 0° C., water (0.2 ml) was added dropwise followed by sodium hydroxide (2.0M, 0.2 ml) and water (0.6 ml). 1% methanol in dichloromethane (10 ml) was added and the mixture filtered through a short pad of arbocel, eluting with 1% methanol in dichloromethane (25 ml). The organic washings were dried over Na2SO4 and concentrated in vacuo to give the title compound as a solid (399 mg, 94%). 1H NMR (400 MHz, CDCl3) δ 7.20 (d, 2H), 7.88 (d, 2H), 4.22-4.34 (m, 1H), 3.70-3.80 (m, 2H), 3.60-4.01 (d, 2H), 2.70-2.88 (m, 3H), 2.64 (s, 2H), 2.32-2.44 (m, 2H) 2.24 (s, 3H), 2.10-2.18 (M, 2H), 1.99-2.08 (m, 2H), 1.79-1.96 (m, 4H), 1.03 (d, 6H).

Workup

  1. customReaction
  2. temperatureThe reaction was then cooled to 0° C.
  3. filtrationthe mixture filtered through a short pad of arbocel
  4. washeluting with 1% methanol in dichloromethane (25 ml)
  5. dry with materialThe organic washings were dried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c040bbc5ed0c4a178feb396d888c8dc7
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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