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

HRID 1432389Notes

Reaction equation

HRID 1432389 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.CCN(CC)CC>C(Cl)Cl.CCCCCC.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 8471TriethylamineHCID 65578Oxalyl chlorideHCID 57395035(2R)-2-[(Triphenylmethyl)amino]butan-1-ol

Product 1

HCID 57714153(R)-2-(Trityl-amino)-butyraldehydeYield 52.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent4×HCID 21584099Diethylether hexaneSolvent

Conditions

Temperature
-45 °C

Procedure

To a stirred solution of DMSO (3.0 mL, 42.28 mmol) in CH2Cl2 (30 mL) under Ar at −45° C., was added oxalyl chloride (2 M in CH2Cl2, 10.56 mL, 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, 15.08 mmol) in CH2Cl2 (30 mL) was added dropwise with stirring. The reaction mixture was sired at this temperature for 3 h, when TLC (8:2 hexane/Et2O) indicated that the reaction had gone to completion. Et3N (10.5 mL, 75.33 mmol) in CH2Cl2 (30 mL) was added and the solution was allowed to warm to RT over 16 h. It was diluted with more CH2Cl2 (200 mL) and washed with H2O (250 mL). The aqueous phase was extracted with CH2Cl2 (3×50 mL) and the combined organic phases washed with brine (50 mL), dried (MgSO4), and evaporated in vacuo. The residue was dissolved in Et2O (30 mL), the solid precipitate was removed by filtration, and the filtrate was evaporated in vacuo. The residue was dissolved in hexane (50 mL), the solid precipitate was removed by filtration, and the filtrate was evaporated in vacuo to afford the title compound as a light yellow oil (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×Bz), 8.77 (d, 1H, J=3.00 Hz, —NHCH(CH2CH3)CHO).

Workup

  1. stirringwith stirring
  2. waitThe reaction mixture was sired at this temperature for 3 h
  3. temperatureto warm to RT over 16 h
  4. washwashed with H2O (250 mL)
  5. extractionThe aqueous phase was extracted with CH2Cl2 (3×50 mL)
  6. washthe combined organic phases washed with brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated in vacuo
  9. dissolutionThe residue was dissolved in Et2O (30 mL)
  10. customthe solid precipitate was removed by filtration
  11. customthe filtrate was evaporated in vacuo
  12. dissolutionThe residue was dissolved in hexane (50 mL)
  13. customthe solid precipitate was removed by filtration
  14. customthe filtrate was evaporated in vacuo

Sources & evidence

ORD record
ord-6e146b74ea2e4dc5b428b27b8d6a8f5d
Source dataset
uspto-grants-2009_11
Patent number
US07612079B2

Reaction notes

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