1-Methylimidazole → 1858268-66-2

HRID 712584Notes

Reaction equation

HRID 712584 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:8])[C@H:5]([CH3:7])[NH2:6].[CH:9]1[CH:14]=[CH:13][C:12]([O:15][P:16](Cl)(Cl)=[O:17])=[CH:11][CH:10]=1.C(N(C(C)C)CC)(C)C.[C:29]([O:43][CH3:44])(=[O:42])[CH2:30][CH2:31][NH:32][C:33](=[O:41])[C@@H:34]([C:36]([CH2:39][OH:40])([CH3:38])[CH3:37])[OH:35].CN1C=CN=C1>ClCCl.CO>[OH:35][C@H:34]([C:36]([CH3:38])([CH3:37])[CH2:39][O:40][P:16]([NH:6][C@@H:5]([CH3:7])[C:4]([O:3][CH3:2])=[O:8])([O:15][C:12]1[CH:13]=[CH:14][CH:9]=[CH:10][CH:11]=1)=[O:17])[C:33]([NH:32][CH2:31][CH2:30][C:29]([O:43][CH3:44])=[O:42])=[O:41]

Participants

8

Reactant 5

HCID 13901-MethylimidazoleHCID 13038Phosphorodichloridic acid, phenyl esterHCID 81531DiisopropylethylamineHCID 135189beta-Alanine, N-(2,4-dihydroxy-3,3-dimethyl-1-oxobutyl)-, methyl ester, (R)-HCID 2733257Alanine methyl ester hydrochloride

Product 1

HCID 718119091858268-66-2Yield 24%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

L-alanine methyl ester hydrochloride (1.35 g, 9.65 mmol) was suspended in dichloromethane (20 mL) and treated with phenyl phosphodichloridate (1.51 mL, 10.15 mmol) at −78° C. under an atmosphere of argon. Diisopropylethylamine (2.6 mL, 20.27 mmol) was added dropwise. The mixture was stirred at −78° C. for 30 minutes, then allowed to warm to room temperature for 1 hr. The mixture was chilled to −5° C. and methyl pantothenate (1.6 mL, 20.27 mmol) was added dropwise in dichloromethane. N-methylimidazole (1.6 mL, 20.27 mmol) was added, and after stirring at −5° C. for 30 mins and room temperature for 1 hour, 2 mL of methanol was added. The mixture was washed sequentially with water (30 mL), 5% citric acid (30 mL), and brine (10 mL). The organic phase was dried (Na2SO4) and the solvent was removed under reduced pressure. Purification was achieved with a 1:1 mixture of EtOAc:hexane to afford the product as a clear colorless oil. (1.1 g, 24% yield). HPLC showed the product, as a 1:1 mixture of disastereomers, having a purity of 97%. 1H NMR (300 MHz, CDCl3): δ 1.11 (s, 3H, CH3), 1.27, 1.39 and 1.40 (2 Ss, 3H, CH3), 1.41 (overlapping d, 3H, J=1.2 Hz, CHCH3), 3.55 (m, 2H, CH2), 3.60 (m, 1H, CH2), 3.63 (m, 1H, CH), 3.66 and 3.68 (2 Ss, 3H, COCH3), 3.70 and 3.74 (2 Ss, 3H, COCH3), 3.78 (m, 1H CH), 4.03 (m, 1H, CH), 4.17 (m, 1H, CH), 7.16 and 7.35 and 7.40 (2 Ms, 5H, Ph). Expected Mol. Wt. 474.18, Observed Mol. Wt. 475.03 (M+H+].

Workup

  1. temperatureto warm to room temperature for 1 hr
  2. temperatureThe mixture was chilled to −5° C.
  3. stirringafter stirring at −5° C. for 30 mins and room temperature for 1 hour
  4. washThe mixture was washed sequentially with water (30 mL), 5% citric acid (30 mL), and brine (10 mL)
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. customthe solvent was removed under reduced pressure
  7. customPurification
  8. additionwas achieved with a 1:1 mixture of EtOAc

Sources & evidence

ORD record
ord-8655d18b6bc04bd1aa156f17602e402d
Source dataset
uspto-grants-2015_11
Patent number
US09181286B2

Reaction notes

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