Sodium Bicarbonate → Boc-Pro-Pro-OH

HRID 2370887Notes

Reaction equation

HRID 2370887 reaction equation
C[O:2][C:3](=[O:23])[C@@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9](=[O:22])[C@@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].C([O-])(O)=O.[Na+]>C1COCC1.O>[C:18]([O:17][C:15]([N:11]1[CH2:12][CH2:13][CH2:14][C@H:10]1[C:9]([N:5]1[CH2:6][CH2:7][CH2:8][C@H:4]1[C:3]([OH:23])=[O:2])=[O:22])=[O:16])([CH3:21])([CH3:19])[CH3:20]

Participants

5

Reactant 2

HCID 516892Sodium BicarbonateHCID 14236281Boc-prolylproline methyl ester

Product 1

HCID 11864387Boc-Pro-Pro-OHYield 89%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

N-tert-butoxycarbonyl L-prolyl L-proline methyl ester 1 (1.10 g, 3.37 mmol) was dissolved in THF (23 mL) and the solution cooled to 0° C. (icebath). LiOH monohydrate (0.156 g, 3.72 mmol) was dissolved in de-ionized H2O (11.5 mL) and the solution cooled to 0° C. before being added dropwise to the solution of 1 over 5 min. The icebath was removed and stirring continued for an additional 3 h 30 min before solid NaHCO3 (0.566 g, 6.74 mmol) was added. Stirring was continued for 20 minutes and the THF evaporated. The solution was diluted with H2O (11.5 mL), washed with Et2O (2×11.5 mL) and acidified to pH 2 by addition of 2M aqueous H2SO4. The resulting solution was extracted with CH2Cl2 (70 mL+4×23 mL). The combined organic extracts were dried with anhydrous MgSO4 and the solvent evaporated affording the title compound as a white solid (0.933 g, 89%) with spectral characteristics in accordance with literature data1; δH(300 MHz; d6-DMSO) 12.41 (1H, br s, COOH), 4.45-4.21 (2H, m, CαH(Pro1)/CαH(Pro2)), 3.73-3.13 (4H, m, CδH2(Pro1)/CδH2(Pro2)), 2.29-1.61 (8H, m, CH2), 1.37/1.30/1.16 (9H, s, (CH3)3, all rotomers); δC (75 MHz; CDCl3) 173.8, 173.5, 173.3, 173.0, 154.6, 153.6, 79.9, 59.6, 59.5, 57.7, 57.6, 47.1, 47.0, 46.9, 46.7, 30.0, 29.2, 28.4, 28.3, 27.7, 27.5, 25.0, 24.2, 23.6; m/z (ESI) 335.1595 ([M+Na]+; C15H24N2O5Na requires 335.1582)

Workup

  1. temperaturethe solution cooled to 0° C.
  2. additionbefore being added dropwise to the solution of 1 over 5 min
  3. customThe icebath was removed
  4. additionwas added
  5. stirringStirring
  6. customthe THF evaporated
  7. additionThe solution was diluted with H2O (11.5 mL)
  8. washwashed with Et2O (2×11.5 mL)
  9. additionacidified to pH 2 by addition of 2M aqueous H2SO4
  10. extractionThe resulting solution was extracted with CH2Cl2 (70 mL+4×23 mL)
  11. dry with materialThe combined organic extracts were dried with anhydrous MgSO4
  12. customthe solvent evaporated

Sources & evidence

ORD record
ord-f595b40552e14926b8446346c7b1a217
Source dataset
uspto-grants-2014_04
Patent number
US08710008B2

Reaction notes

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