Tetrahydrofuran → HCID 15454907, compound

HRID 2287534Notes

Reaction equation

HRID 2287534 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]1[CH2:15][NH:14][C@@H:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C@@H:12]([C:22]([O:24][CH3:25])=[O:23])[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C([O-])(O)=O.[Na+].C1COCC1.[CH:36]1[CH:41]=[CH:40][C:39]([CH2:42][O:43][C:44](Cl)=[O:45])=[CH:38][CH:37]=1>O>[CH2:42]([O:43][C:44]([N:14]1[CH2:15][C@H:10]([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3])[CH2:11][C@H:12]([C:22]([O:24][CH3:25])=[O:23])[C@@H:13]1[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[O:45])[C:39]1[CH:40]=[CH:41][CH:36]=[CH:37][CH:38]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 15454905HCID 15454905, compound

Product 1

HCID 15454907HCID 15454907, compoundYield 102.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred and ice-cooled mixture of (2R*,3S*,5R*)-5-(tert-butyldimethylsilyloxy)methyl-3-methoxycarbonyl-2-phenylpiperidine (4.86 g, 13.4 mmol), NaHCO3 (1.68 g, 20.1 mmol), THF (5.0 ml), and H2O (30.0 ml) was added Cbz-Cl (2.51 g, 14.7 mmol), and the mixture was stirred with ice-cooling for 30 minutes. The mixture was extracted with AcOEt (40.0 ml×3). The combined AcOEt extracts were washed with sat. NaCl aq. solution (×1), dried (MgSO4), and concentrated in vacuo to give a viscous pale yellow oil (6.82 g). This was flash chromatographed over SiO2 (Merck Kieselgel 60, 80.0 g). Elution with n-hexane-AcOEt (30:1/20: 1) gave title compound (6.51 g, 97.9%) as a viscous colorless oil. IRmax (film): 1735(s), 1700(s), 1605(w), 1585(w), 1495(m), 1250(s), 1115(s), 775(s), 740(m), 700(s) cm-1 ; 1H-NMR δ: 7.45-7.31(m, 4H), 7.31-7.15(m, 6H), 6.05(d, J=5.5 Hz, 0.6H), 5.87(d, J=5.5 Hz, 0.4H), 5.32-5.10(5.30, 5.25, 5.21, 5.18, and 5.13; m, 2H), 4.20-4.05(m, 1H), 3.65-3.45(m, 2.4H), 3.60(br.s, 3H), 3.40(dd, J=9.9, 6.6 Hz, 0.6H), 3.08-2.91(m, 1H), 2.63(dd, J=11.7, 11.7 Hz, 0.4H), 2.52(dd, J=13.6, 11.7 Hz, 0.6H), 2.11-1.98(m, 1H), 1.98-1.70(m, 2H), 0.86(s, 3.6H), 0.83(s, 5.4H), 0.026, 0.018, and 0.008(each s, total 6H) ppm.

Workup

  1. temperatureice-cooled
  2. stirringthe mixture was stirred with ice-
  3. temperaturecooling for 30 minutes
  4. extractionThe mixture was extracted with AcOEt (40.0 ml×3)
  5. washThe combined AcOEt extracts were washed with sat. NaCl aq. solution (×1)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4aaca9f50dc8494280888f6e241238bb
Source dataset
uspto-grants-2000_07
Patent number
US06083943

Reaction notes

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