Pyridine → Methyl 2-(1-(benzyloxycarbonyl)-2-methylpyrrolidin-2-yl)benzo[d]oxazole-7-carboxylate

HRID 415271Notes

Reaction equation

HRID 415271 reaction equation
[OH:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[NH:12][C:13]([C:15]1([CH3:30])[CH2:19][CH2:18][CH2:17][N:16]1[C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21])=O.N1C=CC=CC=1.S(Cl)(Cl)=O>C1(C)C=CC=CC=1>[CH2:23]([O:22][C:20]([N:16]1[CH2:17][CH2:18][CH2:19][C:15]1([C:13]1[O:1][C:2]2[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=2[N:12]=1)[CH3:30])=[O:21])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 66621011Benzyl 2-(2-hydroxy-3-(methoxycarbonyl)phenylcarbamoyl)-2-methylpyrrolidine-1-carboxylate

Product 1

HCID 66621299Methyl 2-(1-(benzyloxycarbonyl)-2-methylpyrrolidin-2-yl)benzo[d]oxazole-7-carboxylateYield 32%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of benzyl 2-(2-hydroxy-3-(methoxycarbonyl)phenylcarbamoyl)-2-methylpyrrolidine-1-carboxylate (550 mg, 1.33 mmol) in anhydrous toluene (10 mL) was added anhydrous pyridine (0.583 mL, 7.3 mmol), then thionyl chloride (0.39 mL, 7.3 mmol) was added, the mixture was heated to 110° C. for 6 h. The mixture was cooled to room temperature and poured into ice water (100 mL) carefully with vigorous stirring, then extracted with ethyl acetate (50 mL×3). The organic phase was washed with saturated sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, and concentrated to give crude product. The crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=30:1 to 8:1) to give methyl 2-(1-(benzyloxycarbonyl)-2-methylpyrrolidin-2-yl)benzo[d]oxazole-7-carboxylate (164 mg, yield 32%). 1H-NMR (400 MHz, CDCl3): δ 1.63 (s, 3H) 2.02-2.05 (m, 2H), 2.14-2.16 (m, 1H), 2.40-2.44 (m, 1H), 3.73-3.77 (m, 1H), 3.87-3.90 (m, 1H), 3.94 (s, 3H), 4.71-4.73 (d, J=9.6 Hz, 1H), 5.06-5.09 (m, 2H), 6.79-6.81 (d, J=6 Hz, 1H), 6.89-6.92 (m, 1H), 7.02-7.04 (m, 1H), 7.33-7.37 (m, 3H), 7.80-7.95 (m, 2H); LC-MS (ESI) m/z: 395 (M+1)+.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate (50 mL×3)
  3. washThe organic phase was washed with saturated sodium bicarbonate solution and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customto give crude product
  7. customThe crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=30:1 to 8:1)

Sources & evidence

ORD record
ord-8fd05c0e6f3b47ea905ef480fbdc3b0a
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Reaction notes

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