Trifluoroacetic acid → 5-{2-[2-(3-Chloro-phenyl)-2-hydroxy-ethylamino]-propyl}-benzo[1,3]-dioxole-2,2-dicarboxylic acid bis-methoxycarbonylmethyl ester

HRID 1416742Notes

Reaction equation

HRID 1416742 reaction equation
[CH3:1][O:2][C:3]([CH:5]([O:10][C:11]([C:13]1([C:43]([OH:45])=[O:44])[O:17][C:16]2[CH:18]=[CH:19][C:20]([CH2:22][CH:23]([N:25](C(OC(C)(C)C)=O)[CH2:26][CH:27]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[CH:30]=3)[OH:28])[CH3:24])=[CH:21][C:15]=2[O:14]1)=[O:12])[C:6]([O:8][CH3:9])=[O:7])=[O:4].FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:9][O:8][C:6]([CH:5]([O:10][C:11]([C:13]1([C:43]([OH:45])=[O:44])[O:17][C:16]2[CH:18]=[CH:19][C:20]([CH2:22][CH:23]([NH:25][CH2:26][CH:27]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[CH:30]=3)[OH:28])[CH3:24])=[CH:21][C:15]=2[O:14]1)=[O:12])[C:3]([O:2][CH3:1])=[O:4])=[O:7]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 675816405-(2-{tert-Butoxycarbonyl-[2-(3-chloro-phenyl)-2-hydroxy-ethyl]-amino}-propyl)-benzo[1,3]dioxole-2,2-dicarboxylic acid bis-methoxycarbonyl-methyl ester

Product 1

HCID 544143725-{2-[2-(3-Chloro-phenyl)-2-hydroxy-ethylamino]-propyl}-benzo[1,3]-dioxole-2,2-dicarboxylic acid bis-methoxycarbonylmethyl esterYield 52.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
23 °C

Procedure

To a stirred solution of 5-(2-{tert-butoxycarbonyl-[2-(3-chloro-phenyl)-2-hydroxy-ethyl]-amino}-propyl)-benzo[1,3]dioxole-2,2-dicarboxylic acid bis-methoxycarbonyl-methyl ester (330 mg, 0.50 mmol) and CH2Cl2 (10 mL) was added trifluoroacetic acid (0.08 mL, 113 mg, 0.99 mmol). After stirring at 23° C. for 1 h, additional trifluoroacetic acid (0.08 mL, 113 mg, 0.99 mmol) was added. After a total of 22 h, the mixture was quenched with 5 mL of sat. aq. NaHCO3, and extracted with 3×30 mL of EtOAc. The combined organics were washed with 1×50 mL of brine, dried over MgSO4, filtered and concentrated to a yellow oil. Flash chromatography on silica gel, eluting with CHCl3 /MeOH (20/1 to 10/1) gave 145 mg (52%) of product as a white gum; 1H NMR (300 MHz, CDCl3): δ 1.33 (m, 3H), 1.70-2.40 (brm, 2H), 2.73-2.90 (brt, 1H), 3.04-3.30 (m, 2H), 3.37-3.53 (m, 2H), 3.75 (s, 3H), 3.76 (s, 3H), 4.80 (s, 2H), 4.81 (s, 2H), 5.40 (m, 1H), 6.73-6.93 (complexm, 4H), 7.15-7.32 (m, 2HO, 7.43 (s, 1H); MS (ES) m/z (relative intensity): 566 (M+, 80), 508 (M+ -CO2CH3 +H, 100), 450 (M+ -2CO2CH3 +2H, 30).

Workup

  1. customAfter a total of 22 h, the mixture was quenched with 5 mL of sat. aq. NaHCO3
  2. extractionextracted with 3×30 mL of EtOAc
  3. washThe combined organics were washed with 1×50 mL of brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to a yellow oil
  7. washFlash chromatography on silica gel, eluting with CHCl3 /MeOH (20/1 to 10/1)

Sources & evidence

ORD record
ord-588618e493ed4713b90140dc6c2424d2
Source dataset
uspto-grants-1999_06
Patent number
US05914339

Reaction notes

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