Pyridine → 3-benzyloxy-4-[(S)-2-tert-butoxycarbonyl-1-(methoxy-methyl-carbamoyl)-ethylsulfamoyl]-benzoic acid methyl ester

HRID 1814329Notes

Reaction equation

HRID 1814329 reaction equation
[CH3:1][O:2][C:3](=[O:22])[C:4]1[CH:9]=[CH:8][C:7]([S:10](Cl)(=[O:12])=[O:11])=[C:6]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:5]=1.[C:23]([O:27][C:28](=[O:38])[CH2:29][C@H:30]([NH2:37])[C:31]([N:33]([O:35][CH3:36])[CH3:34])=[O:32])([CH3:26])([CH3:25])[CH3:24].N1C=CC=CC=1>ClCCl.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:22])[C:4]1[CH:9]=[CH:8][C:7]([S:10](=[O:12])(=[O:11])[NH:37][C@H:30]([C:31](=[O:32])[N:33]([O:35][CH3:36])[CH3:34])[CH2:29][C:28]([O:27][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:38])=[C:6]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:5]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 15895197(S)-3-amino-N-methoxy-N-methyl-succinamic acid tert-butyl esterHCID 865882243-Benzyloxy-4-chlorosulfonyl-benzoic acid methyl ester

Product 1

HCID 865882233-benzyloxy-4-[(S)-2-tert-butoxycarbonyl-1-(methoxy-methyl-carbamoyl)-ethylsulfamoyl]-benzoic acid methyl esterYield 56.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-benzyloxy-4-chlorosulfonyl-benzoic acid methyl ester (9.25 g, 27.1 mmol) in dichloromethane (270 mL) was added (S)-3-amino-N-methoxy-N-methyl-succinamic acid tert-butyl ester (6.30 g, 27.1 mmol) followed by pyridine (6.59 mL, 81.4 mmol). The reaction was allowed to stir over night at room temperature. The reaction was then diluted with ethyl acetate (500 mL) 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 an orange oil. The crude residue was chromatographed (silica gel, 40% ethyl acetate-60% hexane) to give 3-benzyloxy-4-[(S)-2-tert-butoxycarbonyl-1-(methoxy-methyl-carbamoyl)-ethylsulfamoyl]-benzoic acid methyl ester as a white foam (8.20 g, 56%). 1H NMR(300 MHz, DMSO) 7.84 (d, 1H), 7.60 (m, 1H), 7.57 (m, 2H), 7.52 (d, 2H), 7.36 (t, 2H), 7.28 (t, 1H), 5.35 (s, 2H), 4.60 (m, 1H), 3.81 (s, 3H), 3.48 (bs, 3H), 2.82 (bs, 3H), 2.46 (dd, 1H), 2.33 (dd, 1H), 1.27 (s, 9H). MS(APCI) m/z 535.2 (M−H).

Workup

  1. washwashed sequentially with 5% citric acid, saturated sodium bicarbonate, and saturated sodium chloride
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto yield an orange oil
  6. customThe crude residue was chromatographed (silica gel, 40% ethyl acetate-60% hexane)

Sources & evidence

ORD record
ord-ba744378360e4dc6b33025a5eb268dc6
Source dataset
uspto-grants-2005_04
Patent number
US06875765B2

Reaction notes

Loading…