Tributylstannane → HCID 11307964, compound

HRID 1003260Notes

Reaction equation

HRID 1003260 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@:10]([C:15]#[C:16][CH2:17]O)([OH:14])[C@@H:9]1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:25]([SnH:29]([CH2:34][CH2:35][CH2:36][CH3:37])[CH2:30][CH2:31][CH2:32][CH3:33])[CH2:26][CH2:27][CH3:28].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1(C)C=CC=CC=1.O1CCCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@:10]2([O:14][CH2:17][C:16]([Sn:29]([CH2:30][CH2:31][CH2:32][CH3:33])([CH2:34][CH2:35][CH2:36][CH3:37])[CH2:25][CH2:26][CH2:27][CH3:28])=[CH:15]2)[C@@H:9]1[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 5948TributylstannaneHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 11301992(2S,3R)-1-tert-Butoxycarbonyl-3-(3-hydroxypropyn-1-yl)-2-phenylpiperidin-3-ol

Product 1

HCID 11307964HCID 11307964, compoundYield 67%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Crude (2S,3R)-1-tert-butoxycarbonyl-3-(3-hydroxypropyn-1-yl)-2-phenylpiperidin-3-ol (Description 18; 45 g) was dissolved in toluene (750 ml) and degassed with nitrogen. Tetrakis(triphenylphosphine) palladium (0) (2.30 g, 2.0 mmol) in toluene (600 ml) was added and the mixture was degassed. Tributyltin hydride (35.78 ml, 38.71 g, 133 mmol) was added dropwise over 15 minutes, with stirring and cooling (internal temperature below 25° C.). The mixture was stirred at room temperature for 1 hour, then the solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (600 ml) and triphenylphosphine (34.88 g, 133 mmol) was added. A solution of diethyl azodicarboxylate (20.94 ml, 23.16 g, 133 mmol) in tetrahydrofuran (150 ml) was added dropwise with stirring and cooling and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure, acetonitrile (600 ml) was added and the mixture was extracted with hexane (8×150 ml). The hexane fractions were combined and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with dichloromethane/ethyl acetate (100:0 increasing to 99:1) to give the title compound as a yellow oil (53.64 g, 67% from (2s,3S)-1-tert-butoxycarbonyl-3-hydroxy-2-phenylpiperidine). 1H NMR (CDCl3) δ 7.38-7.40 (2H, m), 7.15-7.25 (3H, m), 5.96 (1H, t, J 2.3 Hz), 4.93 (1H, s), 4.63 (1H, dd, J 2.23, 12.9 Hz), 4.22 (1H, dd, J 2.23, 12.9 Hz), 4.09-4.14 (1H, m), 3.09-3.17 (1H, m), 1.95-1.99 (1H, m), 1.83-1.86 (1H, m), 1.72-1.76 (2H, m), 1.40-1.51 (6H, m), 1.38 (9H, s), 1.25-1.32 (6H, m), and 0.86-0.99 (15H, m).

Workup

  1. customdegassed with nitrogen
  2. customthe mixture was degassed
  3. temperaturecooling (internal temperature below 25° C.)
  4. stirringThe mixture was stirred at room temperature for 1 hour
  5. customthe solvent was evaporated under reduced pressure
  6. dissolutionThe residue was dissolved in tetrahydrofuran (600 ml)
  7. stirringwith stirring
  8. temperaturecooling
  9. stirringthe mixture was stirred at room temperature for 1 hour
  10. customThe solvent was evaporated under reduced pressure, acetonitrile (600 ml)
  11. additionwas added
  12. extractionthe mixture was extracted with hexane (8×150 ml)
  13. customthe solvent was evaporated under reduced pressure
  14. customThe residue was purified by flash column chromatography on silica gel
  15. washeluting with dichloromethane/ethyl acetate (100:0 increasing to 99:1)

Sources & evidence

ORD record
ord-2e2e53126ed1464fac711096f7313cee
Source dataset
uspto-grants-2000_04
Patent number
US06046195

Reaction notes

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