Triethylamine → (R)-tert-butyl 2-(tosyloxymethyl)morpholine-4-carboxylate

HRID 384719Notes

Reaction equation

HRID 384719 reaction equation
[C:1]1(C)[C:2]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.[OH:12][CH2:13][C@@H:14]1[O:19][CH2:18][CH2:17][N:16]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:15]1.[CH2:27](N(CC)CC)C>CN(C1C=CN=CC=1)C.ClCCl>[S:7]([O:12][CH2:13][C@@H:14]1[O:19][CH2:18][CH2:17][N:16]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:15]1)([C:2]1[CH:1]=[CH:6][C:5]([CH3:27])=[CH:4][CH:3]=1)(=[O:8])=[O:9]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 8623o-Toluenesulfonyl chlorideHCID 1512576(R)-N-Boc-2-hydroxymethylmorpholine

Product 1

HCID 54043639(R)-tert-butyl 2-(tosyloxymethyl)morpholine-4-carboxylateYield 88.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Toluene sulphonyl chloride (0.473, 2.48 mmol) was added to a solution of (R)-tert-butyl 2-(hydroxymethyl)morpholine-4-carboxylate (0.360, 1.65 mmol), triethylamine (0.45 mL, 3.30 mmol) and DMAP (cat.) in dichloromethane (10 mL). The reaction mixture was stirred for 24 h then diluted with dichloromethane (20 mL) and washed sequentially with water (20 mL) and 0.2M HCl (20 mL). The organic phase was dried (Na2SO4) and solvent was removed in vacuo. The crude product was purified by flash column chromatography on silica gel, eluting with ethyl acetate/hexane (1/5), to give the title compound as a colourless solid (0.542 g, 88%).

Workup

  1. washwashed sequentially with water (20 mL) and 0.2M HCl (20 mL)
  2. dry with materialThe organic phase was dried (Na2SO4) and solvent
  3. customwas removed in vacuo
  4. customThe crude product was purified by flash column chromatography on silica gel
  5. washeluting with ethyl acetate/hexane (1/5)

Sources & evidence

ORD record
ord-81b42a7935e0419aa9f05f24d1356684
Source dataset
uspto-grants-2013_02
Patent number
US08367658B2

Reaction notes

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