Lithium Chloride → HCID 68611724, compound

HRID 2095299Notes

Reaction equation

HRID 2095299 reaction equation
[Li+].[Cl-].[BH4-].[Na+].C[O:6][C:7](=O)/[CH:8]=[CH:9]/[CH2:10][C@H:11]1[CH2:13][C@@H:12]1[C:14]1[CH:15]=[N:16][CH:17]=[C:18]([O:20][CH2:21][C@@H:22]2[CH2:25][CH2:24][N:23]2[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH:19]=1>CCO.C1COCC1>[C:29]([O:28][C:26]([N:23]1[CH2:24][CH2:25][C@H:22]1[CH2:21][O:20][C:18]1[CH:19]=[C:14]([C@H:12]2[CH2:13][C@@H:11]2[CH2:10][CH2:9][CH2:8][CH2:7][OH:6])[CH:15]=[N:16][CH:17]=1)=[O:27])([CH3:32])([CH3:31])[CH3:30]

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 4311764Sodium borohydrideHCID 68611718HCID 68611718, compound

Product 1

HCID 68611724HCID 68611724, compoundYield 84.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

LiCl (138 mg, 3.27 mmol, 5.0 equiv.) was added to a stirred solution of NaBH4 (124 mg, 3.27 mol, 5.0 equiv.) in dry EtOH (10 mL) at 0° C., and the mixture was stirred at that temperature for 10 min. Then 4-[(1S,2S)-2-[5-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]cyclopropyl]-2-trans-butenoic acid methyl ester (263 mg, 653 μmol) dissolved in THF (10 mL) was cannulated into the reaction mixture, which was subsequently refluxed for 24 h. The reaction was then quenched cautiously with saturated aqueous NH4Cl solution (10 mL), and the mixture was extracted with EtOAc (2×100 mL). The organic extracts were washed with water (50 mL) and brine (50 mL) and dried over Na2SO4. After concentration in vacuo, the crude product was purified by CC (SiO2, 3-4% MeOH in CH2Cl2 as the eluent) to provide 4-[(1S,2S)-2-[5-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]cyclopropyl]-1-butanol (207 mg, 84%) as a colorless oil. 1H NMR (CDCl3, 300 MHz) δ 8.10 (s, 1H), 8.01 (s, 1H), 6.84 (s, 1H), 4.56-4.43 (m, 1H), 4.37-4.23 (m, 1H), 4.11 (dd, 1H, J=9.8, 3.01 Hz), 3.89 (t, 2H, J=7.3 Hz), 3.66 (t, 2H, J=6.4 Hz), 2.43-2.19 (m, 1H), 1.69-1.45 (m, 7H), 1.41 (s, 9H), 1.12-0.98 (m, 1H), 0.97-0.87 (m, 1H), 0.86-0.76 (m, 1H). MS (ESI) m/z 376 (M+).

Workup

  1. temperaturewas subsequently refluxed for 24 h
  2. customThe reaction was then quenched cautiously with saturated aqueous NH4Cl solution (10 mL)
  3. extractionthe mixture was extracted with EtOAc (2×100 mL)
  4. washThe organic extracts were washed with water (50 mL) and brine (50 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationAfter concentration in vacuo
  7. customthe crude product was purified by CC (SiO2, 3-4% MeOH in CH2Cl2 as the eluent)

Sources & evidence

ORD record
ord-ced531dd2c2f422c8e199e7a86d595e7
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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