4-Methylmorpholine → N-benzyloxy 2(R)-[(3,4-methylendioxybenzyl)-(2,6-dimethyl-4-methoxybenzenesulfonyl)amino]-3-methanesulfonylamino-propionamide

HRID 2298004Notes

Reaction equation

HRID 2298004 reaction equation
[CH2:1]1[O:34][C:33]2[CH:32]=[CH:31][C:5]([CH2:6][N:7]([S:18]([C:21]3[C:26]([CH3:27])=[CH:25][C:24]([O:28][CH3:29])=[CH:23][C:22]=3[CH3:30])(=[O:20])=[O:19])[C@H:8]([CH2:12][NH:13][S:14]([CH3:17])(=[O:16])=[O:15])[C:9]([OH:11])=O)=[CH:4][C:3]=2[O:2]1.[CH2:35]([O:42][NH2:43])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C)C=O>[CH2:35]([O:42][NH:43][C:9](=[O:11])[C@H:8]([N:7]([CH2:6][C:5]1[CH:31]=[CH:32][C:33]2[O:34][CH2:1][O:2][C:3]=2[CH:4]=1)[S:18]([C:21]1[C:26]([CH3:27])=[CH:25][C:24]([O:28][CH3:29])=[CH:23][C:22]=1[CH3:30])(=[O:20])=[O:19])[CH2:12][NH:13][S:14]([CH3:17])(=[O:15])=[O:16])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 102313O-BenzylhydroxylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 183375492(R)-[(3,4-methylendioxybenzyl)-(2,6-dimethyl-4-methoxybenzenesulfonyl)amino]-3-methanesulfonylamino-propionic acid

Product 1

HCID 18337566N-benzyloxy 2(R)-[(3,4-methylendioxybenzyl)-(2,6-dimethyl-4-methoxybenzenesulfonyl)amino]-3-methanesulfonylamino-propionamideYield 50.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 2(R)-[(3,4-methylendioxybenzyl)-(2,6-dimethyl-4-methoxybenzenesulfonyl)amino]-3-methanesulfonylamino-propionic acid (1 g, 1.9 mmol), O-benzylhydroxylamine (0.95 ml, 6 mmol) and 1-hydroxybenzotriazole hydrate (370 mg, 1.9 mmol), and N-methylmorpholine (0.7 ml, 5.7 mmol) in anhydrous dimethylformamide (20 ml) was added 1-ethyl-3(3-dimethylamino)-propyl carbodiimide hydrochloride salt. The mixture was stirred overnight and then condensed on the roto-evaporator. The remainder was taken up in ethyl acetate (60 ml) and partitioned with an equal volume of 5% aqueous hydrochloric acid. The ethyl acetate phase was collected and washed consecutively with equal volumes of 5% sodium bicarbonate and brine. The aqueous phases were back extracted with ethyl acetate (2×60 ml) and the organic layers combined, dried with magnesium sulfate, filtered and condensed. The residue was purified by preparative thin layer chromatography using 65% ethyl acetate-hexanes as eluant providing N-benzyloxy 2(R)-[(3,4-methylendioxybenzyl)-(2,6-dimethyl-4-methoxybenzenesulfonyl)amino]-3-methanesulfonylamino-propionamide as a yellow viscous oil (591 mg).

Workup

  1. customcondensed
  2. customon the roto-evaporator
  3. custompartitioned with an equal volume of 5% aqueous hydrochloric acid
  4. customThe ethyl acetate phase was collected
  5. washwashed consecutively with equal volumes of 5% sodium bicarbonate and brine
  6. extractionThe aqueous phases were back extracted with ethyl acetate (2×60 ml)
  7. dry with materialdried with magnesium sulfate
  8. filtrationfiltered
  9. customcondensed
  10. customThe residue was purified by preparative thin layer chromatography

Sources & evidence

ORD record
ord-090a2ee0debe484cb93c6344d62febdb
Source dataset
uspto-grants-2002_12
Patent number
US06492394B1

Reaction notes

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