1,2-Dichloroethane → 3,3-dimethyl-2-(phenylmethoxycarbonylamino)butanoic acid

HRID 2191204Notes

Reaction equation

HRID 2191204 reaction equation
C[N:2]1[C:9](=[O:10])CC(=O)N(C)C1=O.N[C:13]1[CH:36]=[CH:35][C:16]([C:17](NC(C(C)(C)C)C(N2CCCC2C(O)=O)=O)=[O:18])=[CH:15][C:14]=1Cl.C(N([CH:44]([CH3:46])[CH3:45])CC)(C)C.[CH2:47](Cl)CCl.CC[O:53][C:54]([CH3:56])=[O:55]>C(Cl)Cl.CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:17]([O:18][C:9]([NH:2][CH:56]([C:44]([CH3:46])([CH3:47])[CH3:45])[C:54]([OH:53])=[O:55])=[O:10])[C:16]1[CH:15]=[CH:14][CH:13]=[CH:36][CH:35]=1

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 8857Ethyl AcetateHCID 69860Dimethylbarbituric acidHCID 81531DiisopropylethylamineHCID 10156704851091-96-8

Product 1

HCID 34012063,3-dimethyl-2-(phenylmethoxycarbonylamino)butanoic acidYield 77%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 6 (5.05 g, 22.0 mmol) in CH2Cl2 (50 mL) at 0° C. was added 1,3-dimethylbarbituric acid (DMBA) (3.78 g, 24.2 mmol)and Pd(PPh3)4 (0.15 g, 0.13 mmol). After 10 minutes, a solution of 5 (8.40 g, 22.0 mmol) in DMF (25 mL) was added followed by diisopropylethylamine (DIPEA) (7.66 mL, 44.1 mmol), (2.98 g, 22.0 mmol) and EDC (5.06 g, 26.4 mmol). The solution was stirred at 0° C. for 10 minutes then at room temperature for 18 hours. The reaction was diluted with EtOAc (200 mL), washed with 0.5N NaHSO4 (2×200 mL), 10% NaHCO3 (2×200 mL), saturated NaCl (1×150 mL), dried over anhydrous MgSO4, and evaporated to dryness. Flash column chromatography on silica gel using CH2Cl2/MeOH, (99/1 to 98/2%) afforded the title compound as a white solid (11.20 g, 77% yield): 1H-NMR (500 MHz, CDCl3) δ 1.08 (s, 9H), 1.27 (t, 3H), 1.85-1.99 (m, 1H), 2.00-2.06 (m. 1H), 2.07-2.18 (m, 1H), 2.32-2.48 (m, 2H), 2.78-2.89 (m, 1H), 3.62-3.76 (m, 2H), 3.82-3.96 (m, 2H), 4.39 (s, 1H), 4.54-4.60 (m, 1H), 4.62-4.76 (m, 1H), 4.85 (d, 1H), 6.57 (d, 1H), 6.73 (d, 1H), 7.38 (d, 1H), 7.49 (d, 1H), 7.72 (s, 1H). Analytical HPLC (cyano column): 13.10 min. LC-MS (ES+) m/e=509.4 (M+H), m.p.=96-99° C.

Workup

  1. waitat room temperature for 18 hours
  2. washwashed with 0.5N NaHSO4 (2×200 mL), 10% NaHCO3 (2×200 mL), saturated NaCl (1×150 mL)
  3. dry with materialdried over anhydrous MgSO4
  4. customevaporated to dryness

Sources & evidence

ORD record
ord-fcaac962108f42319c47ea8945090568
Source dataset
uspto-grants-2012_12
Patent number
US08329662B2

Reaction notes

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