Sodium Bicarbonate → N-tert-butoxycarbonyl O-benzyl L-seryl L-valyl L-valine

HRID 2370900Notes

Reaction equation

HRID 2370900 reaction equation
C[O:2][C:3](=[O:36])[C@H:4]([CH:33]([CH3:35])[CH3:34])[NH:5][C:6](=[O:32])[C@H:7]([CH:29]([CH3:31])[CH3:30])[NH:8][C:9](=[O:28])[C@H:10]([CH2:19][O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].C([O-])(O)=O.[Na+]>C1COCC1.O.CCOC(C)=O>[C:15]([O:14][C:12]([NH:11][C@H:10]([C:9]([NH:8][C@H:7]([C:6]([NH:5][C@H:4]([C:3]([OH:36])=[O:2])[CH:33]([CH3:34])[CH3:35])=[O:32])[CH:29]([CH3:31])[CH3:30])=[O:28])[CH2:19][O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:13])([CH3:16])([CH3:18])[CH3:17]

Participants

6

Reactant 2

HCID 516892Sodium BicarbonateHCID 86671351N-tert-butoxycarbonyl O-benzyl L-seryl L-valyl L-valine methyl ester2×

Product 1

HCID 86671355N-tert-butoxycarbonyl O-benzyl L-seryl L-valyl L-valineYield 42%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

N-tert-butoxycarbonyl O-benzyl L-seryl L-valyl L-valine methyl ester 13 (14.60 g, 28.76 mmol) was dissolved in THF (220 mL) and the solution cooled to 0° C. (icebath). LiOH monohydrate (1.33 g, 31.7 mmol) was dissolved in de-ionized water (110 mL). The solution was cooled to 0° C. (icebath) and added dropwise to the solution of 13 over 25 min. The reaction mixture was stirred for an additional 2 h 35 min before solid NaHCO3 (4.83 g, 57.5 mmol) was added and the bulk of THF evaporated. The solution was diluted with water (220 mL) and washed with Et2O (2×220 mL). The solution was then acidified to pH 2 by addition of 2 M aqueous H2SO4 and extracted with EtOAc (3×350 mL). The combined organic fractions were dried with anhydrous MgSO4 and the solvent evaporated affording a slightly yellowish liquid. The residue was redissolved in EtOAc and precipitated by addition of hexane. The solvent was decanted off and the residue dried affording the title compound as an off-white solid (5.95 g, 42%); δH (200 MHz; d6-DMSO) 12.52 (1H, br s, COOH), 8.03 (1H, d, J 8, NH(Valx)), 7.65 (1H, d, J 9, NH(Valy)), 7.36-7.23 (5H, m, Ph), 7.10 (1H, d, J 8, NH(Ser(Bn)), 4.46 (2H, s, CH2Ph), 4.36 (1H, dd, J 7 and 9, CαH(Valy)), 4.28-4.22 (1H, m, CαH(Ser(Bn))), 4.10 (1H, dd, J 6 and 8, CαH(Valx)), 3.64-3.54 (2H, m, CH2), 2.08-1.91 (2H, m, CH(CH3)2), 1.38 (9H, s, (CH3)2), 0.88-0.80 (12H, m, CH3); δC (75 MHz; d6-DMSO) 172.6, 170.9, 169.4, 155.1, 138.1, 128.0, 127.4, 127.3, 78.3, 71.9, 69.8, 57.2, 56.8, 54.6, 31.1, 29.5, 28.1, 19.0, 18.9, 18.0, 17.7; m/z (ESI) 516.2663 ([M+Na]+; C25H39N3O7Na requires 516.2685)

Workup

  1. temperatureThe solution was cooled to 0° C. (icebath)
  2. additionwas added
  3. customthe bulk of THF evaporated
  4. additionThe solution was diluted with water (220 mL)
  5. washwashed with Et2O (2×220 mL)
  6. additionThe solution was then acidified to pH 2 by addition of 2 M aqueous H2SO4
  7. extractionextracted with EtOAc (3×350 mL)
  8. dry with materialThe combined organic fractions were dried with anhydrous MgSO4
  9. customthe solvent evaporated
  10. customaffording a slightly yellowish liquid
  11. customprecipitated by addition of hexane
  12. customThe solvent was decanted off
  13. customthe residue dried

Sources & evidence

ORD record
ord-0d9aed18fa9a4034ab5f3d65ed370723
Source dataset
uspto-grants-2014_04
Patent number
US08710008B2

Reaction notes

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