4-Nitrobenzenesulfonyl chloride → (S)-3-{(R)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-2-(4-nitro-benzenesulfonylamino)-propionic acid methyl ester

HRID 391844Notes

Reaction equation

HRID 391844 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:34])[C@@H:5]([NH2:33])[CH2:6][C:7]1[CH:32]=[CH:31][C:10]2[O:11][C@H:12]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=4)=[CH:17][CH:16]=3)[CH2:13][O:14][C:9]=2[CH:8]=1.C([O-])(O)=O.[Na+].[N+:40]([C:43]1[CH:48]=[CH:47][C:46]([S:49](Cl)(=[O:51])=[O:50])=[CH:45][CH:44]=1)([O-:42])=[O:41]>CCOC(C)=O>[CH3:2][O:3][C:4](=[O:34])[C@@H:5]([NH:33][S:49]([C:46]1[CH:45]=[CH:44][C:43]([N+:40]([O-:42])=[O:41])=[CH:48][CH:47]=1)(=[O:50])=[O:51])[CH2:6][C:7]1[CH:32]=[CH:31][C:10]2[O:11][C@H:12]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=4)=[CH:17][CH:16]=3)[CH2:13][O:14][C:9]=2[CH:8]=1

Participants

5

Reactant 3

HCID 74044-Nitrobenzenesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 66719251(S)-2-Amino-3-{(R)-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-propionic acid methyl ester hydrochloride

Product 1

HCID 58327446(S)-3-{(R)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-2-(4-nitro-benzenesulfonylamino)-propionic acid methyl esterYield 110.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

(S)-2-Amino-3-{(R)-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-propionic acid methyl ester hydrochloride (1.2 g) was dissolved in 100 mL EtOAc and 100 mL saturated aqueous NaHCO3 and 1.0 g p-nitrobenzenesulfonyl chloride was added. After stirring at room temperature for 2 hours, the layers were separated and the organic layer was dried over Na2SO4 and evaporated. The residue was purified by silica gel flash chromatography (hexanes to 7:3 hexanes/EtOAc) to give 1.7 g desired product after drying. 1H NMR (400 MHz, CDCl3): 8.27 (m, 2H), 7.89 (m, 2H), 7.54 (d, 1H), 7.45 (d, 1H), 7.35 (m, 2H), 7.28-7.24 (m, 1H), 7.20 (m, 2H), 6.81 (m, 1H), 6.56 (m, 2H) 5.26 (m, 1H), 5.02 (s, 2H), 4.99 (m, 1H), 4.26 (m, 2H), 3.95 (m, 1H), 3.66 (s, 3H), 3.05-2.85 (m, 2H).

Workup

  1. customthe layers were separated
  2. dry with materialthe organic layer was dried over Na2SO4
  3. customevaporated
  4. customThe residue was purified by silica gel flash chromatography (hexanes to 7:3 hexanes/EtOAc)

Sources & evidence

ORD record
ord-fda477b93d61435ca375db56e851ed52
Source dataset
uspto-grants-2013_02
Patent number
US08383644B2

Reaction notes

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