Tetrahydrofuran → HCID 56847971, compound

HRID 1798426Notes

Reaction equation

HRID 1798426 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:11])[C@H:6]([CH:8]([CH3:10])[CH3:9])[NH2:7])[CH3:3].S=C1N([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][C:29](=[O:31])[CH3:30])=[C:24]([O:32][CH3:33])[CH:23]=2)=[O:19])CCS1.C1COCC1.C(N(C(C)C)CC)(C)C>CO.C(Cl)Cl>[C:29]([O:28][C:25]1[CH:26]=[CH:27][C:22]([CH2:21][O:20][C:18]([NH:7][CH:6]([CH:8]([CH3:10])[CH3:9])[C:5]([O:4][CH2:2][CH3:3])=[O:11])=[O:19])=[CH:23][C:24]=1[O:32][CH3:33])(=[O:31])[CH3:30]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 81531Diisopropylethylamine2×HCID 87181Ethyl L-valinate hydrochloride2×HCID 568478684-(Acetyloxy)-3-methoxybenzyl 2-thioxo-1,3-thiazolidine-3-carboxylate

Product 1

HCID 56847971HCID 56847971, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 887MethanolCatalystHCID 6344DichloromethaneSolvent

Procedure

L-Valine ethyl ester hydrochloride (122.5 mg, 1.05×0.642 mmol) and thiazolide VII (219.2 mg, 0.642 mmol) were covered with THF (3.2 mL). To the stirred suspension was added diisopropylethylamine (166 mg, 224 μL, 2×0.642 mmol). The reaction mixture was stirred overnight. A second portion of diisopropylethylamine and four drops of anhydrous methanol were added, and the mixture was stirred for four days. A second portion of portion of valine ethyl ester hydrochloride was added, and the reaction mixture was stirred for two more days, after which time the solution was clear and colorless. The reaction solution was diluted with CH2Cl2 and extracted with 1N HCl and saturated NaCl. The organic layer was dried over anhydrous MgSO4, filtered, concentrated, and dried well under vacuum. The crude material was covered with four mL of hexanes/ethyl acetate (7:3, v/v) causing the released MTA to separate. The supernatant was drawn of, the crystals rinsed twice with fresh 7:3 hexanes/ethyl acetate, the rinsings were combined with the original supernatant, and the resulting volume concentrated. The product was purified by column chromatography on silica gel using hexanes/ethyl acetate (7:3, v/v) as eluant to give 165.8 mg (71%) of a colorless oil: Rf=0.36 (hexanes/ethyl acetate, 7:3, v/v); 1HNMR (CDCl3) δ 6.99 (d, 3J=8 Hz, 1H), 6.96 (s, 1H), 6.92 (bd, 3J=8 Hz, 1H), 5.26 (d, 8.15 Hz, 1H), 5.06 (s, 2H), 4.28-4.24 (m, 1H), 4.23-4.15 (m, 2H), 3.82 (s, 3H), 2.29 (s, 3H), 2.18-2.11 (m, 1H), 1.26 (t, 3J=7 Hz, 3H), 0.95 (d, 3J=6.8 Hz, 3H) and 0.88 (d, 6.8 Hz, 3H). Exact mass (ESI) calculated for C18H25NO7Na [M+Na]=390.1523. found 390.1515.

Workup

  1. stirringthe mixture was stirred for four days
  2. stirringthe reaction mixture was stirred for two more days
  3. extractionextracted with 1N HCl and saturated NaCl
  4. dry with materialThe organic layer was dried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customdried well under vacuum
  8. customto separate
  9. washrinsed twice with fresh 7:3 hexanes/ethyl acetate
  10. concentrationthe resulting volume concentrated
  11. customThe product was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-8607f046776a4193bb5bde4e7e9c452b
Source dataset
uspto-grants-2013_01
Patent number
US08343971B2

Reaction notes

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