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

HRID 81433Notes

Reaction equation

HRID 81433 reaction equation
S(C)C.[C:4]([Li])([CH3:7])([CH3:6])[CH3:5].[C:9]([NH:28][C@@H:29]([CH2:32][CH3:33])[CH:30]=[O:31])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[NH4+].[Cl-]>CCOCC>[CH3:5][C:4]([CH3:7])([CH:30]([OH:31])[C@@H:29]([NH:28][C:9]([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH2:32][CH3:33])[CH3:6]

Participants

6

Reactant 4

HCID 1068Dimethyl SulfideHCID 25517Ammonium ChlorideHCID 57452676(S)-2-(tritylamino)butanalHCID 178418306HCID 178418306, compound

Product 1

HCID 57714164(3RS,4S)-2,2-dimethyl-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 tert-butyl lithium (1.5 M in pentane, 8.0 mL, 4 eq, 12.0 mmol) dropwise and the solution allowed to warm to room temperature. The mixture was recooled to −55° 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, 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: Et2O (100:0→90:10) to afford the title compound as a light yellow oil. Yield: 0.47 g (40%). (53% de 3R,4S: 47% de 3S,4S). 1H-NMR (d6-DMSO, 250 MHz): δ 0.37 & 0.87 (2×t, 3H, J=7.46 Hz, —NHCH(CH2CH3)CH(C(CH3)3)OH), 0.58 & 0.71 (2×s, 9H, —NHCH(CH2CH3)CH(C(CH3)3)OH), 1.38-1.52 (m, 2H, —NHCH(CH2CH3)CH(C(CH3)3)OH), 2.00 (m, 1H, —NHCH(CH2CH3)CH(C(CH3)3)OH), 2.28 (m, 1H, —NHCH(CH2CH3)CH(C(CH3)3)OH), 2.95 (m, 1H, —NHCH(CH2CH3)CH(C(CH3)3)OH), 4.24 & 4.79 (2×d, 1H, J=5.21 & 6.16 Hz, —NHCH(CH2CH3)CH(C(CH3)3)OH), 7.15-7.53 (m, 15H, 3×Ph).

Workup

  1. customwas recooled to −55° C., to which
  2. stirringstirred at this temperature for 3 h
  3. temperatureto warm to room temperature over 16 h
  4. extractionThe reaction mixture was extracted with Et2O (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: Et2O (100:0→90:10)

Sources & evidence

ORD record
ord-ef0d2ada7b7042e3b7bb794236eb95e7
Source dataset
uspto-grants-2014_09
Patent number
US08846696B2

Reaction notes

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