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

HRID 2370898Notes

Reaction equation

HRID 2370898 reaction equation
C[O:2][C:3](=[O:32])[C@H:4]([CH:29]([CH3:31])[CH3:30])[NH:5][C:6](=[O:28])[C@H:7]([CH:25]([CH3:27])[CH3:26])[NH:8][C:9](=[O:24])[C@H:10]([CH2:19][O:20][CH2:21][CH:22]=[CH2:23])[NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].C([O-])(O)=O.[Na+]>C1COCC1.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:32])=[O:2])[CH:29]([CH3:30])[CH3:31])=[O:28])[CH:25]([CH3:27])[CH3:26])=[O:24])[CH2:19][O:20][CH2:21][CH:22]=[CH2:23])=[O:13])([CH3:16])([CH3:18])[CH3:17]

Participants

5

Reactant 2

HCID 516892Sodium BicarbonateHCID 86671348N-tert-butoxycarbonyl O-allyl L-seryl L-valyl L-valine methyl ester

Product 1

HCID 86671352N-tert-butoxycarbonyl O-allyl L-seryl L-valyl L-valineYield 71%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

N-tert-butoxycarbonyl O-allyl L-seryl L-valyl L-valine methyl ester (8) (10.21 g, 22.31 mmol) was dissolved in THF (170 mL). The solution was cooled to 0° C. (icebath). LiOH monohydrate (1.03 g, 24.6 mmol) was dissolved in de-ionized water (85 mL) and the solution cooled to 0° C. The solution was then added dropwise to the solution of 8 over 20 min. The reaction mixture was stirred for an additional 2 h 40 min at 0° C. Solid NaHCO3 (3.75 g, 44.6 mmol) was added and the mixture stirred for 5 min before the THF was evaporated. The solution was diluted with water (170 mL), washed with Et2O (2×170 mL), acidified to pH 2 by addition of 2 M aqueous H2SO4 and extracted with EtOAc (3×250 mL). The combined organic fractions were dried with anhydrous MgSO4 and the solvent evaporated affording the title compound as a white solid (7.00 g, 71%); δH (300 MHz; d6-DMSO) 12.53 (1H, br s, COOH), 8.00 (1H, d, J 8, NH (Valx)), 7.62 (1H, d, J 9, NH(Valy)), 7.02 (1H, d, J 8, NH (Ser(All))), 5.84 (1H, ddt, J 5, 10 and 17, CH═CH2), 5.23 (1H, ddt, J 1, 3 and 17, CH═CHH)), 5.12 (1H, ddt, J 1, 3 and 10, CH═CHH), 4.34 (1H, dd, J 7 and 9, CαH(Valy)), 4.21-4.15 (1H, m, CαH(Ser(All))), 4.10 (1H, dd, J 6 and 8, CαH(Valx)), 3.92 (2H, dt, J 1 and 5, CH2CH═CH2), 3.59-3.45 (2H, m, CH2), 2.06-1.91 (2H, m, CH(CH3)2), 1.38 (9H, s, (CH3)3), 0.90-0.80 (12H, m, CH3); δC (75 MHz; d6-DMSO) 172.6, 170.9, 169.5, 155.1, 134.9, 116.3, 78.2, 71.0, 69.5, 57.2, 56.9, 54.6, 31.1, 29.6, 28.1, 19.0, 19.0, 17.9, 17.7; m/z (ESI) 466.2518 ([M+Na]+; C21H37N3O7Na requires 466.2529)

Workup

  1. temperaturethe solution cooled to 0° C
  2. additionThe solution was then added dropwise to the solution of 8 over 20 min
  3. customwas evaporated
  4. additionThe solution was diluted with water (170 mL)
  5. washwashed with Et2O (2×170 mL)
  6. additionacidified to pH 2 by addition of 2 M aqueous H2SO4
  7. extractionextracted with EtOAc (3×250 mL)
  8. dry with materialThe combined organic fractions were dried with anhydrous MgSO4
  9. customthe solvent evaporated

Sources & evidence

ORD record
ord-7c95e5b7dd1949d387ef7a2c6839c4c7
Source dataset
uspto-grants-2014_04
Patent number
US08710008B2

Reaction notes

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