Water → HCID 15454906, compound

HRID 2287527Notes

Reaction equation

HRID 2287527 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+].O.Cl[C:33]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:34]>C1COCC1.CCOC(C)=O>[CH2:36]([O:35][C:33]([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:34])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 15454904HCID 15454904, compound

Product 1

HCID 15454906HCID 15454906, compoundYield 105.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred and ice-cooled mixture of (2R*,3S*,5S*)-5-(tert-butyldimethylsilyloxy)methyl-3-methoxycarbonyl-2-phenylpiperidine (11.46 g, 31.52 mmol), NaHCO3 (3.97 g, 47.3 mmol), H2O (80.0 ml), and THF (10.0 ml) was added a solution of benzyl chloroformate (Cbz-Cl, 5.92 g, 34.67 mmol) in THF (15.0 ml). A precipitated gummy material was dispersed by adding AcOEt (40.0 ml). After the resultant milky suspension was stirred with ice-cooling for 2.5 hours, the organic layer was separated from the mixture, and the aqueous layer was extracted with AcOEt (40 ml×4). The combined organic layer and AcOEt extracts were washed with sat. NaCl aq. solution (×1), dried (MgSO4), and concentrated in vacuo to give a yellow oil (16.56 g). This was flash chromatographed over Sir (Merck Kieselgel 60, 200 g). Elution with n-hexane-AcOEt (60:1/30:1/20:1) gave title compound (13.88 g, 88.5%) as a pale yellow oil. IRmax (film): 1735(s), 1700(s), 1498(m), 1290(s), 1253(s), 1100(s), 775(s), 740(m), 700(s) cm-1 ; 1H-NMR δ: 7.42-7.28(m, 6H), 7.28-7.16(m, 4H), 5.98-5.87(m, 1H), 5.31-5.10(m, 2H), 3.92(dm, J=13.6 Hz, 1H), 3.63(dd, J=10.1, 9.7 Hz, 1H), 3.60(s, 3H), 3.53(dd, J=10.1, 7.9 Hz, 1H), 3.09(ddd, J=11.2, 5.6, 5.6 Hz, 1H), 3.12-2.95(m, 1H), 2.24-2.06(m, 1H), 2.06-1.93(m, 1H), 0.87(s, 9H), 0.02(s, 6H) ppm.

Workup

  1. temperatureice-cooled
  2. additionA precipitated gummy material was dispersed
  3. stirringAfter the resultant milky suspension was stirred with ice-
  4. temperaturecooling for 2.5 hours
  5. customthe organic layer was separated from the mixture
  6. extractionthe aqueous layer was extracted with AcOEt (40 ml×4)
  7. washThe combined organic layer and AcOEt extracts were washed with sat. NaCl aq. solution (×1)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2ea353937fb94e7796703ec6e6589909
Source dataset
uspto-grants-2000_07
Patent number
US06083943

Reaction notes

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