4-Methylmorpholine → 3-(2-benzyloxy-4-carbamoyl-benzenesulfonylamino)-N-methoxy-N-methyl-succinamic acid tert-butyl ester

HRID 1814331Notes

Reaction equation

HRID 1814331 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][C:17]=1[S:18](=[O:36])(=[O:35])[NH:19][C@H:20]([C:29](=[O:34])[N:30]([O:32][CH3:33])[CH3:31])[CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:12](O)=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[N:38]1CCOCC1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[OH-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[C:25]([O:24][C:22](=[O:23])[CH2:21][CH:20]([NH:19][S:18]([C:17]1[CH:16]=[CH:15][C:11]([C:12](=[O:13])[NH2:38])=[CH:10][C:9]=1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)(=[O:35])=[O:36])[C:29]([N:30]([O:32][CH3:33])[CH3:31])=[O:34])([CH3:28])([CH3:26])[CH3:27]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 14923Ammonium HydroxideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 865882253-benzyloxy-4-[(S)-2-tert-butoxycarbonyl-1-(methoxy-methyl-carbamoyl)-ethylsulfamoyl]-benzoic acid

Product 1

HCID 865882263-(2-benzyloxy-4-carbamoyl-benzenesulfonylamino)-N-methoxy-N-methyl-succinamic acid tert-butyl esterYield 82.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-benzyloxy-4-[(S)-2-tert-butoxycarbonyl-1-(methoxy-methyl-carbamoyl)-ethylsulfamoyl]-benzoic acid (8.0 g, 15.3 mmol) in tetrahydrofuran (150 ml) at 0° C. was added 4-methyl morpholine (2.5 ml, 22.9 mmol), 1-hydroxybenzotriazole (3.09 g, 22.90 mmol), followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4.40 g, 22.90 mmol). The reaction was stirred for 1 h at 0° C., then concentrated ammonium hydroxide was added (3.1 ml, 22.9 mmol). The reaction was allowed to warm slowly to room temperature and stirred overnight. The reaction was then diluted with ethyl acetate and washed sequentially with 5% citric acid, saturated sodium bicarbonate, and saturated sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield a pale oil. The crude residue was chromatographed (silica gel with a gradient of 50% ethyl acetate/49% hexane/1% acetic acid to 99% ethyl acetate/1% acetic acid) to give 3-(2-benzyloxy-4-carbamoyl-benzenesulfonylamino)-N-methoxy-N-methyl-succinamic acid tert-butyl ester as a white foam (6.57 g, 82%). 1H NMR(300 MHz, DMSO) 8.12 (s, 1H), 7.76 (d, 1H), 7.38 (m, 9H), 5.34 (dd, 2H), 4.60 (m, 1H), 3.50 (bs, 3H), 2.58 (bs, 3H), 2.55 (dd, 1H), 2.34 (dd, 1H), 1.30 (s, 9H). MS(APCI) m/z 522.2 (M+1), 520.2 (M−H).

Workup

  1. temperatureto warm slowly to room temperature
  2. stirringstirred overnight
  3. washwashed sequentially with 5% citric acid, saturated sodium bicarbonate, and saturated sodium chloride
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto yield a pale oil
  8. customThe crude residue was chromatographed (silica gel with a gradient of 50% ethyl acetate/49% hexane/1% acetic acid to 99% ethyl acetate/1% acetic acid)

Sources & evidence

ORD record
ord-02b23bfc0581458ba6466373665ad52f
Source dataset
uspto-grants-2005_04
Patent number
US06875765B2

Reaction notes

Loading…