Diisopropylethylamine → HCID 67158148, compound

HRID 549934Notes

Reaction equation

HRID 549934 reaction equation
Cl.Cl.[NH:3]1[CH2:8][CH2:7][CH2:6][C@@H:5]([CH2:9][N:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:17])[CH2:12][CH2:11]2)[CH2:4]1.C(N([CH:32]([CH3:34])[CH3:33])CC)(C)C.C(OC1(O[Si](C)(C)C)CC1)C.C([BH3-])#N.[Na+]>CO.C1COCC1.C(O)(=O)C>[CH:32]1([N:3]2[CH2:8][CH2:7][CH2:6][C@H:5]([CH2:9][N:10]3[CH2:11][CH2:12][N:13]([C:16]([O:18][CH2:19][C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)=[O:17])[CH2:14][CH2:15]3)[CH2:4]2)[CH2:34][CH2:33]1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 67158366HCID 67158366, compound

Product 1

HCID 67158148HCID 67158148, compoundYield 62%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
81 °C

Procedure

Benzyl 4-[(3R)-piperidin-3-ylmethyl]piperazine-1-carboxylate dihydrochloride (389 mg) was dissolved in MeOH (5 mL) and di-isopropylethylamine (0.52 mL) added under argon. Freshly dried 3 Å molecular sieves (413 mg) were added, followed sequentially by glacial acetic acid (0.2 mL), 1-ethoxy-1-trimethylsilyloxycyclopropane (1.2 mL) and sodium cyanoborohydride as a 1M solution in THF (4.5 mL). The mixture was heated at 81° C. for 2 hours, allowed to cool, filtered through Celite, washed through with 1:1 MeOH-THF (10 mL) and evaporated. The residue was partitioned between ethyl acetate and 1M aqueous sodium hydroxide solution, the organic extract washed with brine, dried over MgSO4 and evaporated. The residue was purified by silica column chromatography, eluting with a gradient of 0 to 10% MeOH in dichloromethane to give the title compound as a white solid (222 mg, 62%).

Workup

  1. additionFreshly dried 3 Å molecular sieves (413 mg) were added
  2. temperatureto cool
  3. filtrationfiltered through Celite
  4. washwashed through with 1:1 MeOH-THF (10 mL)
  5. customevaporated
  6. customThe residue was partitioned between ethyl acetate and 1M aqueous sodium hydroxide solution
  7. extractionthe organic extract
  8. washwashed with brine
  9. dry with materialdried over MgSO4
  10. customevaporated
  11. customThe residue was purified by silica column chromatography
  12. washeluting with a gradient of 0 to 10% MeOH in dichloromethane

Sources & evidence

ORD record
ord-a37e75e9126742c89a7d6aa52689a8a1
Source dataset
uspto-grants-2011_05
Patent number
US07943768B2

Reaction notes

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