Dimethylformamide → 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

HRID 1416741Notes

Reaction equation

HRID 1416741 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:27][CH:28]([C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[CH:31]=1)[OH:29])[CH:9]([CH3:26])[CH2:10][C:11]1[CH:25]=[CH:24][C:14]2[O:15][C:16]([C:21]([OH:23])=[O:22])([C:18]([OH:20])=[O:19])[O:17][C:13]=2[CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:37]([O-:40])([O-:39])=O.[K+].[K+].[CH3:43][O:44][C:45](=[O:48])[CH2:46]Br.[CH3:49]N(C=O)C>>[CH3:49][O:39][C:37]([CH:46]([O:19][C:18]([C:16]1([C:21]([OH:23])=[O:22])[O:15][C:14]2[CH:24]=[CH:25][C:11]([CH2:10][CH:9]([N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:27][CH:28]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[CH:31]=3)[OH:29])[CH3:26])=[CH:12][C:13]=2[O:17]1)=[O:20])[C:45]([O:44][CH3:43])=[O:48])=[O:40]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 60984Methyl bromoacetateHCID 538189185-(2-{tert-Butoxycarbonyl-[2-(3-chloro-phenyl)-2-hydroxy-ethyl]-amino}-propyl)-benzo[1,3]dioxole-2,2-dicarboxylic acid

Product 1

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 esterYield 79%

Conditions

Temperature
50 °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 (500 mg, 0.96 mmol) and DMF (10 mL) was added K2CO3 (132 mg, 0.96 mmol) and methyl-2-bromoacetate (0.23 mL, 366 mg, 2.40 mmol). After stirring at 50° C. for 4 h, the reaction mixture was cooled to 23° C., quenched with 5 mL sat. aq. NaHCO3, and extracted with 3×30 mL of EtOAc. The combined organics were washed with 2×50 mL brine, dried over MgSO4, filtered and concentrated to a yellow oil. Flash chromatography on silica gel, eluting with hexane/EtOAc (4/1 to 2/1), gave 508 mg (79%) of product as a colorless oil; 1H NMR (300 MHz, CDCl3): δ 1.22 (d, J=6.9 Hz, 3H), 1.41 (brs, 9H), 2.50-2.60 (brm, 1H), 2.60-2.75 (brm, 1H), 3.06-3.15 (brm, 1H), 3.45-3.60 (brm, 1H), 3.76 (s, 3H), 3.77 (s, 3H), 4.05-4.20 (brm, 1H), 4.70-4.79 (brm, 1H), 4.79(s, 2H), 4.80(s, 2H), 5.42-5.51 (brs, 1H), 6.60-6.91 (complexm, 4H), 7.20-7.43(complexm, 3H); MS (ES) m/z (relative intensity): 666 (M+, (100), 610 (25).

Workup

  1. temperaturethe reaction mixture was cooled to 23° C.
  2. customquenched with 5 mL sat. aq. NaHCO3
  3. extractionextracted with 3×30 mL of EtOAc
  4. washThe combined organics were washed with 2×50 mL brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to a yellow oil
  8. washFlash chromatography on silica gel, eluting with hexane/EtOAc (4/1 to 2/1)

Sources & evidence

ORD record
ord-7c026e052acd4d88a572e32981cb46f5
Source dataset
uspto-grants-1999_06
Patent number
US05914339

Reaction notes

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