4-Methylmorpholine → HCID 14039196, compound

HRID 648429Notes

Reaction equation

HRID 648429 reaction equation
[C:1]([NH:8][C@H:9]([C:14]([OH:16])=O)[CH2:10][CH:11]([CH3:13])[CH3:12])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C[N:18]1[CH2:23][CH2:22][O:21]CC1.ClC([O:27][CH2:28][CH:29]([CH3:31])[CH3:30])=O.C(N(CC)CC)C.[OH-:39].[Na+].O1C[CH2:44][CH2:43][CH2:42]1>O1CCOCC1.O.CO.O>[NH:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[C@H:9]([C:14]([NH:18][CH:23]([C:22]([OH:21])=[O:39])[CH:28]([OH:27])[C:29]1[CH:31]=[CH:44][CH:43]=[CH:42][CH:30]=1)=[O:16])[CH2:10][CH:11]([CH3:12])[CH3:13]

Participants

10

Reactant 6

HCID 79724-MethylmorpholineHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 62365Isobutyl chloroformateHCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-

Product 1

HCID 14039196HCID 14039196, compoundYield 94%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A solution of 1.7 g (0.0075 mol) of Boc-Leucine in 30 ml of dry tetrahydrofuran was cooled to -5° C. and 0.99 g (0.0089 mol) of N-methylmorpholine and 1.0 g (0.0075 mol) of isobutyl chloroformate were added and stirred for 1 h. A solution of compound 1 (3.0 g, 0.0075 mol) in 10 ml of dioxane:water (7:3) (v/v) containing (0.0089 mol) 0.909 g of triethylamine was added. The mixture was stirred for 3 at ambient temperature, approximately 20 ml water was added and the tetrahydrofuran was evaporated in vacuo. The resulting oil was extracted with ethyl acetate (80 ml) and the pooled extracts were washed sequentially with 1N-hydrochloric acid, sat'd sodium bicarbonate solution, sat'd sodium chloride solution and dried over anhydrous Na2SO4. The solvent was removed in vacuo yielding an oil: 2.9 g (0.007 mol, yield 94%); homogeneous on TLC Rf (A) 0.91, Rf (B) 0.70). The resulting ester was dissolved in 20 ml of methanol and 20 ml of 1N sodium hydroxide was added. The mixture was stirred for 3 h at ambient temperatures and then concentrated in vacuo. The aqueous solution was acidified with 4N-hydrochloric acid while stirring on ice and then extracted with ethyl acetate. The pooled extracts were washed with sat'd sodium chloride, dried over sodium sulfate and evaporated in vacuo to yield a clear oil: (2.7 g, 95% yield; Rf (A) 0.79, Rf (B) 0.83; [α]D25 -22.2° (c 1, MeOH); H1NMR (CDCl3) δ: 0.95 (m, 7H, H3C--CH--CH3), 1.17(m, 2H, CH2) 1.4 (s, 9H, Boc), 2.15(m, 1H, NH--CH--C(O)) 4.05(d, 1H, CH--COH), 4.15(d, 1H, CH--COOH), 4.6 (s, 1H, OH, exchanged by D2O), 4.75(d, 1H, C(O)--NH, exchanged by D2O) 4.8(d, 1H, C(O)--NH, exchanged D2O, 7.3(s, 5H, ArH), 9.5(b, 1H, COOH) Anal. Calcd for C20H30O6N2 : C 60.91, H, 7.61N, 7.10., Found: C, 60.89H, 7.62, N, 7.08.

Workup

  1. additionwas added
  2. stirringThe mixture was stirred for 3 at ambient temperature
  3. customthe tetrahydrofuran was evaporated in vacuo
  4. extractionThe resulting oil was extracted with ethyl acetate (80 ml)
  5. washthe pooled extracts were washed sequentially with 1N-hydrochloric acid
  6. dry with materialdried over anhydrous Na2SO4
  7. customThe solvent was removed in vacuo
  8. customyielding an oil
  9. stirringThe mixture was stirred for 3 h at ambient temperatures
  10. concentrationconcentrated in vacuo
  11. stirringwhile stirring on ice
  12. extractionextracted with ethyl acetate
  13. washThe pooled extracts were washed with sat'd sodium chloride
  14. dry with materialdried over sodium sulfate
  15. customevaporated in vacuo
  16. customto yield a clear oil

Sources & evidence

ORD record
ord-590dcc89f8904375bfaea82023aeb57a
Source dataset
uspto-grants-1988_04
Patent number
US04735651

Reaction notes

Loading…