Sodium Bicarbonate → N-tert-butoxycarbonyl O-allyl L-seryl alpha,alpha-dimethylglycyl L-valine

HRID 2370899Notes

Reaction equation

HRID 2370899 reaction equation
C[O:2][C:3](=[O:31])[C@H:4]([CH:28]([CH3:30])[CH3:29])[NH:5][C:6](=[O:27])[C:7]([CH3:26])([CH3:25])[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:7]([CH3:25])([CH3:26])[C:6]([NH:5][C@H:4]([C:3]([OH:31])=[O:2])[CH:28]([CH3:29])[CH3:30])=[O:27])=[O:24])[CH2:19][O:20][CH2:21][CH:22]=[CH2:23])=[O:13])([CH3:16])([CH3:17])[CH3:18]

Participants

5

Reactant 2

HCID 516892Sodium BicarbonateHCID 86671354N-(tert-Butoxycarbonyl)-O-allyl-L-seryl-alpha-aminoisobutyryl-L-valine methyl ester2×

Product 1

HCID 86671353N-tert-butoxycarbonyl O-allyl L-seryl alpha,alpha-dimethylglycyl L-valineYield 88.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

N-tert-butoxycarbonyl O-allyl L-seryl α,α-dimethylglycyl L-valine methyl ester 12 (8.56 g, 19.3 mmol) was dissolved in THF (150 mL). The solution was cooled to 0° C. (icebath). LiOH monohydrate (0.891 g, 21.2 mmol) was dissolved in de-ionized water (75 mL) and the solution cooled to 0° C. The solution was added dropwise to the solution of 12 over 20 min. The reaction mixture was stirred for an additional 2 h 40 min before solid NaHCO3 (3.24 g, 38.6 mmol) was added. The mixture was stirred for 5 min and the bulk of THF evaporated. The solution was diluted with water (150 mL), washed with Et2O (2×150 mL), acidified to pH 2 by addition of 2 M aqueous H2SO4 and extracted with EtOAc (3×300 mL). The combined organic fractions were dried with anhydrous MgSO4 and the solvent evaporated affording the title compound as a white solid (7.30 g, 88%); δH (300 MHz; d6-DMSO) 12.62 (1H, br s, COOH), 8.01 (1H, s, NH(Aib)), 7.12 (1H, d, J 9, NH(Val)), 6.85 (1H, d, J 8, NH(Ser(All))), 5.92-5.79 (1H, m, CH═CH2), 5.29-5.21 (1H, m, CH═CHH), 5.15-5.10 (1H, m, CH═CHH), 4.19-4.10 (2H, m, CαH(Ser(All))/CαH(Val)), 3.94 (2H, dt, J 1 and 5, CH2CH═CH2), 3.57-3.45 (2H, m, CH2), 2.08-1.97 (1H, m, CH(CH3)2), 1.38 (12H, s, CH3(Aib)/(CH3)3), 1.35 (3H, s, CH3(Aib)), 0.84 (3H, d, J 7, CH3(Val)), 0.81 (3H, d, J 7, CH3(Val)); δC (75 MHz; d6-DMSO): 173.6, 172.7, 169.5, 155.1, 134.9, 116.3, 78.2, 70.9, 69.5, 57.0, 56.1, 54.4, 30.1, 28.1, 25.7, 23.8, 19.0, 17.8; m/z (ESI) 452.2357 ([M+Na]+; C20H35N3O7Na requires 452.2372)

Workup

  1. temperaturethe solution cooled to 0° C
  2. additionwas added
  3. customthe bulk of THF evaporated
  4. additionThe solution was diluted with water (150 mL)
  5. washwashed with Et2O (2×150 mL)
  6. additionacidified to pH 2 by addition of 2 M aqueous H2SO4
  7. extractionextracted with EtOAc (3×300 mL)
  8. dry with materialThe combined organic fractions were dried with anhydrous MgSO4
  9. customthe solvent evaporated

Sources & evidence

ORD record
ord-1b8475e2a3f04f099fe68122b1d3b8a3
Source dataset
uspto-grants-2014_04
Patent number
US08710008B2

Reaction notes

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