Dimethyl Sulfide → (2S,3R)-3-(trityl-amino)-pentan-2-ol

HRID 1984262Notes

Reaction equation

HRID 1984262 reaction equation
S(C)C.[CH3:4][Li].[C:6]([NH:25][C@H:26]([CH2:29][CH3:30])[CH:27]=[O:28])([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[NH4+].[Cl-]>CCOCC.CCCCCC>[C:6]([NH:25][C@H:26]([CH2:29][CH3:30])[C@@H:27]([OH:28])[CH3:4])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 1068Dimethyl SulfideHCID 25517Ammonium ChlorideHCID 57714153(R)-2-(Trityl-amino)-butyraldehydeHCID 178418348HCID 178418348, compound

Product 1

HCID 57714160(2S,3R)-3-(trityl-amino)-pentan-2-ol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent3×HCID 8058HexaneSolvent

Procedure

To a stirred suspension of CuBr.SMe2 (2.74 g, 2.2 eq, 13.33 mmol) in Et2O (100 mL) under an argon atmosphere at −70° C., was added methyllithium (1.6 M in Et2O, 16.6 mL, 4.4 eq, 26.56 mmol) dropwise, and the solution allowed to warm to room temperature. The mixture was recooled to −70° C., to which was added a solution of (R)-2-(trityl-amino)-butyraldehyde (2 g, 1 eq, 6.05 mmol) in Et2O (25 mL) dropwise with stirring. The reaction mixture was stirred at this temperature for 2 h, when TLC (hexane:ether; 80:20) indicated that the reaction had gone to completion. To the reaction mixture was added a saturated aqueous solution of NH4Cl (100 mL) and allowed to warm to room temperature over 16 h. The reaction mixture was extracted with ether (2×200 mL), and the combined organic phase washed with brine (50 mL), dried (MgSO4) and evaporated in vacuo. The residue was purified by silica gel column chromatography, eluted with hexane:ether (80:20) to afford the title compound as a light yellow oil. Yield: 1.91 g (91%). (80% de 2S,3R: 20% de 2R,3R). 1H-NMR (d6-DMSO, 250 MHz): δ 0.47 & 0.55 (2×t, J=7.43 & 7.27 Hz, —NHCH(CH2CH3) CH(CH3)OH), 0.99-1.12 (m, 5H, —NHCH(CH2CH3)CH(CH3)OH), 2.03 (m, 1H, —NHCH(CH2CH3)CH(CH3)OH), 3.32-3.51 (m, 1H, —NHCH(CH2CH3) CH(CH3)OH), 4.40 (d, 1H, J=3.79 Hz, —NHCH(CH2CH3)CH(CH3)OH), 7.14-7.51 (m, 15H, 3×Ph).

Workup

  1. customwas recooled to −70° C., to which
  2. stirringThe reaction mixture was stirred at this temperature for 2 h
  3. temperatureto warm to room temperature over 16 h
  4. extractionThe reaction mixture was extracted with ether (2×200 mL)
  5. washthe combined organic phase washed with brine (50 mL)
  6. dry with materialdried (MgSO4)
  7. customevaporated in vacuo
  8. customThe residue was purified by silica gel column chromatography
  9. washeluted with hexane:ether (80:20)

Sources & evidence

ORD record
ord-4a73af50cecd483995736ae565f09613
Source dataset
uspto-grants-2009_06
Patent number
US07544689B2

Reaction notes

Loading…