Dimethyl Sulfide → (3RS,4S)-2-methyl-4-(trityl-amino)-hexan-3-ol

HRID 81431Notes

Reaction equation

HRID 81431 reaction equation
S(C)C.[CH:4]([Li])([CH3:6])[CH3:5].[C:8]([NH:27][C@@H:28]([CH2:31][CH3:32])[CH:29]=[O:30])([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[NH4+].[Cl-]>CCOCC>[CH3:5][CH:4]([CH:29]([OH:30])[C@@H:28]([NH:27][C:8]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:31][CH3:32])[CH3:6]

Participants

6

Reactant 4

HCID 1068Dimethyl SulfideHCID 25517Ammonium ChlorideHCID 57452676(S)-2-(tritylamino)butanalHCID 178506895HCID 178506895, compound

Product 1

HCID 57714148(3RS,4S)-2-methyl-4-(trityl-amino)-hexan-3-ol

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a stirred suspension of CuBr.SMe2 (1.37 g, 2.2 eq, 6.66 mmol) in Et2O (100 mL) under an argon atmosphere at −78° C., was added isopropyllithium (0.7 M in pentane, 17.29 mL, 4 eq, 12.1 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 (S)-2-(trityl-amino)-butyraldehyde (1 g, 1 eq, 3.03 mmol) in Et2O (25 mL) dropwise with stirring. The reaction mixture was stirred at this temperature for 1 h, then allowed to warm to −55° C. and stirred at this temperature for 3 h. 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 Et2O (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 (100:0→90:10) to afford the title compound as a colourless oil; Yield: 0.36 g (32%). (50% de 3R,4S: 50% de 3S,4S). 1H-NMR (d6-DMSO, 250 MHz): δ 0.44 (t, 3H, J=6.79 Hz, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 0.52 & 0.76 (2×d, 6H, J=6.63 Hz, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 0.80-1.15 (m, 2H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 1.70 (m, 1H, —NHCH(CH2CH3)CH(CH (CH3)2)OH), 2.10 (m, 1H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 2.76 (m, 1H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 2.99 (m, 1H, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 4.55 (d, 1H, J=5.84 Hz, —NHCH(CH2CH3)CH(CH(CH3)2)OH), 7.17-7.46 (m, 15H, 3×Ph).

Workup

  1. customwas recooled to −70° C., to which
  2. stirringThe reaction mixture was stirred at this temperature for 1 h
  3. temperatureto warm to −55° C.
  4. stirringstirred at this temperature for 3 h
  5. temperatureto warm to room temperature over 16 h
  6. extractionThe reaction mixture was extracted with Et2O (2×200 mL)
  7. washthe combined organic phase washed with brine (50 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated in vacuo
  10. customThe residue was purified by silica gel column chromatography
  11. washeluted with hexane:ether (100:0→90:10)

Sources & evidence

ORD record
ord-a5f4a76d25744ff5a12866a250bf358d
Source dataset
uspto-grants-2014_09
Patent number
US08846696B2

Reaction notes

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