Lithium hydroxide, monohydrate → HCID 22137606, compound

HRID 1827336Notes

Reaction equation

HRID 1827336 reaction equation
[CH:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)=O.[CH3:16][CH2:17][O:18][C:19](/[C:21](/P(OCC)(OCC)=O)=[CH:22]\[CH3:23])=[O:20].O[Li].O>C1COCC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[CH2:17]([O:18][C:19](=[O:20])/[CH:21]=[CH:22]/[CH:23]=[CH:1]/[CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)[CH3:16]

Participants

6

Reactant 3

HCID 168937Lithium hydroxide, monohydrateHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 6272114HCID 6272114, compound

Product 1

HCID 22137606HCID 22137606, compoundYield 95.3%

Reagents, catalysts & solvents 2

HCID 311Citric AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of the above aldehyde (21) (2.10 g, 10 mmol), triethyl trans-4-phosphono-2-butenoate (3.0 g, 12 mmol), LiOH—H2O (510 mg, 12 mmol) and 4A molecular sieve (5 g) in THF (100 mL) was heated at reflux 1.5 hours. The molecular sieve was filtered through a short pad of Celite and washed with EtOAc (100 mL) and the filtrate concentrated to give sticky brown oil. The oily residue was diluted with 5% citric acid and extracted thrice with 100 mL of EtOAc. The combined extracts were washed with NaHCO3, brine, then dried over Na2SO4 and concentrated. Purification by flash chromatography (EtOAc:Hexanes=1:5) gave a white solid (22) (2.95 g, 95%) of the desired compound. 1H NMR (500 MHz, CDCL3) δ 7.24 (dd, J=15.5, 10.5 Hz, 1H), 6.16 (dd, J=15.5, 10.5 Hz, 1H), 6.04 (dd, J=15.5, 7.0 Hz, 1H), 5.82 (d, J=15.5 Hz, 1H), 4.20 (q, J=7.0 Hz, 2H), 4.10 (m, 2H), 2.75 (m, 2H), 2.25 (m, 1H), 1.71 (m, 2H), 1.46 (s, 9H), 1.34 (m, 2H), 1.29 (t, J=7.0 Hz, 3H); MS (ESI+) m/z 210.75 (M+H+-boc).

Workup

  1. temperaturewas heated
  2. temperatureat reflux 1.5 hours
  3. filtrationThe molecular sieve was filtered through a short pad of Celite
  4. washwashed with EtOAc (100 mL)
  5. concentrationthe filtrate concentrated
  6. customto give sticky brown oil
  7. extractionextracted thrice with 100 mL of EtOAc
  8. washThe combined extracts were washed with NaHCO3, brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customPurification by flash chromatography (EtOAc:Hexanes=1:5)

Sources & evidence

ORD record
ord-99c20f04f631454d9b79c50d95a224f4
Source dataset
uspto-grants-2006_05
Patent number
US07053214B2

Reaction notes

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