HCID 18388390, compound → HCID 18723469, compound

HRID 842214Notes

Reaction equation

HRID 842214 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([C:13](OCC)=[O:14])[CH:10]([C:18]([N:20]2[CH2:25][CH2:24][CH:23]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[CH2:22][CH2:21]2)=O)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1.CCOCC>[CH2:1]([N:8]1[CH2:12][CH:11]([CH2:13][OH:14])[CH:10]([CH2:18][N:20]2[CH2:21][CH2:22][CH:23]([C:26]3[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=3)[CH2:24][CH2:25]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 18388390HCID 18388390, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 18723469HCID 18723469, compoundYield 84.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 6.4 g (14.6 mmol) of 1-benzyl-3-(RS)-(4-(4-fluorophenyl)piperidinylcarbonyl)-4-(RS)-(ethoxycarbonyl)pyrrolidine in 60 mL of THF at 0° C. was added 17.5 mL (17.5 mmol) of a 1M solution of lithium aluminum hydride (LAH) in ether and the reaction was stirred at 0° C. for 30 min. The reaction mixture was quenched with SN NaOH. The reaction mixture was extracted with ether and the combined organic fractions were washed with 5N NaOH solution. The organic fractions were dried over Na2SO4, filtered and the filtrate was purified by chromatography [silica, hexanes:ethyl acetate:(2N NH3 in MeOH), 10:10:1] to give 4.7 g of the title compound. Spectrum (ESI) m/e=383 (M+1). 1H NMR (CDCl3) δc7.31-7.33 (m, 4 H), 7.26-7.28 (m, 1H), 7.16-7.19 (m, 2H), 6.97 (t, 2H, J=8.5 Hz), 3.63-3.66 (m, 2H), 3.57 (d, 1H, J=13Hz), 3.43 (t, 1H, J=10 Hz), 3.22 (d, 1H, J=11 Hz),2.97 (d, 1H, J=11 Hz), 2.80 (d of d, 1H, J=8.5, 7.5 Hz), 2.76 (t, 1H, J=9 Hz), 2.12-2.54 (m, 8 H), 2.02 (t of d, 1H, J=2.5, 12 Hz), 1.75-1.85 (m, 5H).

Workup

  1. customThe reaction mixture was quenched with SN NaOH
  2. extractionThe reaction mixture was extracted with ether
  3. washthe combined organic fractions were washed with 5N NaOH solution
  4. dry with materialThe organic fractions were dried over Na2SO4
  5. filtrationfiltered
  6. customthe filtrate was purified by chromatography [silica, hexanes:ethyl acetate:(2N NH3 in MeOH), 10:10:1]

Sources & evidence

ORD record
ord-0346babc7eb34aa5bea9ab2a382f7cb3
Source dataset
uspto-grants-2002_04
Patent number
US06372764B1

Reaction notes

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