Water → (S)-N-[(2R,3S)-2-methyl-3-tetrahydropyranyloxybutylidene]-p-toluenesulfinamide

HRID 2113401Notes

Reaction equation

HRID 2113401 reaction equation
[C:1]1([CH3:10])[CH:6]=[CH:5][C:4]([S@@:7]([NH2:9])=[O:8])=[CH:3][CH:2]=1.[CH3:11][C@@H:12]([C@@H:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=CC=1)[CH3:16])[CH:13]=O.[OH2:25]>ClCCl>[CH3:13][C@@H:12]([C@@H:15]([O:17][CH:18]1[CH2:19][CH2:24][CH2:23][CH2:22][O:25]1)[CH3:16])[CH:11]=[N:9][S@:7]([C:4]1[CH:5]=[CH:6][C:1]([CH3:10])=[CH:2][CH:3]=1)=[O:8]

Participants

5

Reactant 3

HCID 962WaterHCID 11116285(S)-4-methylbenzenesulfinamideHCID 86590269(2S,3S)-2-methyl-3-benzyloxybutyraldehyde

Product 1

HCID 69214407(S)-N-[(2R,3S)-2-methyl-3-tetrahydropyranyloxybutylidene]-p-toluenesulfinamideYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Ti(OEt)4 (1.71 g, 1.57 ml, 7.5 mmol, 5 eq.) was added dropwise, at room temperature, to a mixture of (S)-(+)-p-toluenesulfinamide (233 mg, 1.50 mmol) and (2S,3S)-2-methyl-3-benzyloxybutyraldehyde (6) (280 mg, 1.50 mmol) in dichloromethane (25 ml). The solution was refluxed under argon for 5.5 hours. The reaction was neutralized at 0° C. adding water (25 ml). The cloudy solution was filtered on Celite and the filter cake was washed with dichloromethane (2×25 ml). The phases were separated, the aqueous phase was extracted with dichloromethane and the combined organic portions were dried over Na2SO4 and they were concentrated. Flash chromatography on a silica gel column (heptane/EtOAc=6:1) produced (S)-N-[(2R,3S)-2-methyl-3-tetrahydropyranyloxybutylidene]-p-toluenesulfinamide (7) (375 mg, 77%): IR (CHCl3) 3010, 2976, 2946, 2878, 2854, 1620, 1598, 1494, 1455, 1443, 1380, 1354, 1214 cm−1; 1H NMR (250 MHz, CDCl3) δ 8.31 (d, J=5.8 Hz, 0.5H); 8.23 (d, J=5.3 Hz, 0.5H); 7.55 (m, 2H); 7.29 (m, 2H); 4.79 to 4.70 (m, 0.5H); 4.55 to 4.51 (m, 0.5H); 4.00 to 3.82 (m, 1.5H); 3.77 to 3.70 (m, 0.5H); 3.48 to 3.41 (m, 1H); 2.84 to 2.64 (m, 1H); 2.39 (s, 3H); 1.78 to 1.41 (m, 6H); 1.25 (d, J=6.4 Hz, 1.5H); 1.14 (d, J=5.7 Hz, 3H); 1.14 (d, J=7.1 Hz, 1.5H); 1.09 (d, J=7.0 Hz, 1.5H); 13C NMR (75 MHz, CDCl3) δ 169.2; 168.6; 141.9; 141.8; 141.2; 129.4; 124.4; 124.2; 99.6; 94.6; 76.4; 72.2; 62.3; 61.8; 45.6; 45.2; 30.6; 30.5; 25.2; 25.2; 21.1; 19.4; 19.1; 18.9; 16.3; 13.0; 12.5; MS (CI) m/z 324 [M+H]+. HRMS: calculated for C17H26NO3S (M+H), 324.16333; found, 324.16141.

Workup

  1. temperatureThe solution was refluxed under argon for 5.5 hours
  2. customwas neutralized at 0° C.
  3. filtrationThe cloudy solution was filtered on Celite
  4. washthe filter cake was washed with dichloromethane (2×25 ml)
  5. customThe phases were separated
  6. extractionthe aqueous phase was extracted with dichloromethane
  7. dry with materialthe combined organic portions were dried over Na2SO4 and they
  8. concentrationwere concentrated

Sources & evidence

ORD record
ord-089d717d7e6445e696dfdc6c45581bb7
Source dataset
uspto-grants-2008_10
Patent number
US07432087B2

Reaction notes

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