Dimethyl Sulfoxide → (R)-2-(Trityl-amino)-butyraldehyde

HRID 81424

Reaction equation

HRID 81424 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[C:11]([NH:30][C@H:31]([CH2:34][CH3:35])[CH2:32][OH:33])([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CCCCCC>C(Cl)Cl.CCOCC>[C:11]([NH:30][C@H:31]([CH2:34][CH3:35])[CH:32]=[O:33])([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8058HexaneHCID 65578Oxalyl chlorideHCID 57395035(2R)-2-[(Triphenylmethyl)amino]butan-1-ol

Product 1

HCID 57714153(R)-2-(Trityl-amino)-butyraldehyde

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent4×

Conditions

Temperature
-45 °C

Procedure

To a stirred solution of DMSO (3.0 mL, 2.8 eq, 42.28 mmol) in DCM (30 mL) under an argon atmosphere at −45° C., was added oxalyl chloride (2 M in DCM, 10.56 mL, 1.40 eq, 21.12 mmol), dropwise. The reaction mixture was stirred at −45° C. for 1 h, after which time a solution of (R)-2-(trityl-amino)-butan-1-ol (5 g, 1 eq, 15.08 mmol) in DCM (30 mL) was added dropwise with stirring. The reaction mixture was stirred at this temperature for 3 h, when TLC (hexane:ether; 80:20) indicated that the reaction had gone to completion. To the reaction mixture was added a solution of TEA (10.5 mL, 5 eq, 75.33 mmol) in DCM (30 mL), and the solution allowed to warm to room temperature over 16 h. The reaction mixture was diluted with more DCM (200 mL) and washed with water (250 mL). The aqueous phase was extracted with DCM (3×50 mL), and the combined organic phase washed with brine (50 mL), dried (MgSO4) and evaporated in vacuo. The residue was dissolved in ether (30 mL), the solid precipitate removed by filtration and the filtrate was evaporated in vacuo. The residue was dissolved in hexane (50 mL), the solid precipitate removed by filtration and the filtrate was evaporated in vacuo to afford the title compound as a light yellow oil. Yield: 2.59 g (52%). 1H-NMR (d6-DMSO, 250 MHz): δ 0.77 (t, 3H, J=7.42 Hz, —NHCH(CH2CH3)CHO), 1.34-1.61 (m, 2H, —NHCH(CH2CH3)CHO), 2.92 (m, 1H, —NHCH(CH2CH3)CHO), 3.62 (d, 1H, J=8.21 Hz, —NHCH(CH2CH3)CHO), 7.16-7.46 (m, 15H, 3×Ph), 8.77 (d, 1H, J=3.00 Hz, —NHCH(CH2CH3)CHO).

Workup

  1. stirringwith stirring
  2. stirringThe reaction mixture was stirred at this temperature for 3 h
  3. temperatureto warm to room temperature over 16 h
  4. washwashed with water (250 mL)
  5. extractionThe aqueous phase was extracted with DCM (3×50 mL)
  6. washthe combined organic phase washed with brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated in vacuo
  9. dissolutionThe residue was dissolved in ether (30 mL)
  10. customthe solid precipitate removed by filtration
  11. customthe filtrate was evaporated in vacuo
  12. dissolutionThe residue was dissolved in hexane (50 mL)
  13. customthe solid precipitate removed by filtration
  14. customthe filtrate was evaporated in vacuo

Sources & evidence

ORD record
ord-d8db7c4b260e46d2adf106ecab333cbf
Source dataset
uspto-grants-2014_09
Patent number
US08846696B2

Linked notes

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