Triethylamine → (S)-3-ethyl-4-tosylmorpholine

HRID 72178Notes

Reaction equation

HRID 72178 reaction equation
[OH:1][CH2:2][C@@H:3]([NH:6][S:7]([C:10]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=1)(=[O:9])=[O:8])[CH2:4][CH3:5].[CH2:17](N(CC)CC)[CH3:18].FC(F)(F)S([O-])(=O)=O.C1([S+](C2C=CC=CC=2)C=C)C=CC=CC=1.[NH4+].[Cl-]>ClCCl>[CH2:4]([C@H:3]1[CH2:2][O:1][CH2:18][CH2:17][N:6]1[S:7]([C:10]1[CH:11]=[CH:12][C:13]([CH3:16])=[CH:14][CH:15]=1)(=[O:9])=[O:8])[CH3:5]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 110211032-(Tosylamino)butan-1-olHCID 12003642Sulfonium, ethenyldiphenyl-, 1,1,1-trifluoromethanesulfonate (1:1)

Product 1

HCID 58222512(S)-3-ethyl-4-tosylmorpholine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

(S)—N-(1-hydroxybutan-2-yl)-4-methylbenzene-sulfonamide (800 mg, 3 mmol) was dissolved in dichloromethane (20 mL) and triethylamine (0.92 mL, 6.6 mmol) was added. The mixture was stirred at 0° C. for 10 minutes. Diphenyl(vinyl)sulfonium trifluoromethanesulfonate (1.25 g, 3.45 mmol), dissolved in dichloromethane (10 mL) was added dropwise over 5 minutes. The mixture was stirred while allowed to warm up to room temperature overnight. Saturated aqueous NH4Cl was added and the phases were separated. The aqueous phase was extracted with 2×30 mL of DCM. The combined organic phases were dried with MgSO4 and filtered. The filtrate was concentrated on silica gel and purified by flash chromatography (100% Hex to 60% EtOAc/Hex) to give (S)-3-ethyl-4-tosylmorpholine (j-3) as a white solid: 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J=8.3 Hz, 2H), 7.30 (t, J=8.3 Hz, 2H), 3.77-3.60 (m, 3H), 3.60-3.44 (m, 2H), 3.44-3.19 (m, 3H), 2.43 (s, 3H), 1.67 (dtd, J=28.6, 14.0, 7.4 Hz, 2H), 1.31-1.12 (m, 2H), 0.97-0.84 (m, 3H); LC-MS: m/z=270 (M+H).

Workup

  1. additionwas added dropwise over 5 minutes
  2. stirringThe mixture was stirred while
  3. temperatureto warm up to room temperature overnight
  4. customthe phases were separated
  5. extractionThe aqueous phase was extracted with 2×30 mL of DCM
  6. dry with materialThe combined organic phases were dried with MgSO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated on silica gel
  9. custompurified by flash chromatography (100% Hex to 60% EtOAc/Hex)

Sources & evidence

ORD record
ord-6d191ccad8ee4e3aa43d1db4dbb481ca
Source dataset
uspto-grants-2014_09
Patent number
US08828990B2

Reaction notes

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