4-Methylmorpholine → N-Boc-(D)-methioninyl sarcosine benzyl ester

HRID 377460Notes

Reaction equation

HRID 377460 reaction equation
[C:1]([NH:8][C@@H:9]([C:14]([OH:16])=O)[CH2:10][CH2:11][S:12][CH3:13])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].S(C1C=CC(C)=CC=1)(O)(=O)=O.[CH2:28]([O:35][C:36](=[O:40])[CH2:37][NH:38][CH3:39])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN1CCOCC1>C(#N)C.C(OCC)(=O)C.CN(C)C=O>[CH2:28]([O:35][C:36](=[O:40])[CH2:37][N:38]([C:14](=[O:16])[C@@H:9]([CH2:10][CH2:11][S:12][CH3:13])[NH:8][C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH3:39])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 111051N-(tert-Butyloxycarbonyl)-D-methionineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 12210899Sar-OBzl p-tosylate

Product 1

HCID 86751714N-Boc-(D)-methioninyl sarcosine benzyl esterYield 92.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-Boc-(D)-methionine (17.1 g, 68.58 mmole) and sarcosine benzyl ester tosylate salt (24.08 g, 68.60 mmole) were suspended in 110 mL of acetonitrile and 25 mL of dimethylformamide at 0° C., then benzotriazol-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (30.34 g, 68.58 mmole) and N-methylmorpholine (20.83 g, 205.83 mmole) were added. The ice bath was removed after 30 minutes and the reaction was stirred for 18 hours at room temperature. The reaction mixture was reduced in volume under vacuum at 25° C. to give an oil. The oil was dissolved in ethyl acetate (250 mL), then successively washed with 1N hydrochloric acid (1×50 mL), saturated sodium bicarbonate (1×50 mL) and brine (1×50 mL). The organic layer was dried with anhydrous magnesium sulfate and evaporated under vacuum to give crude product. The crude product was purified by column chromatography on silica gel, eluting with 60:40 hexane:ethyl acetate to yield 26.07 g (92.6%) of the title compound as an oil. Thin layer chromatography analysis of the title compound showed a single spot with Rf=0.55 (silica, 3:2 ethyl acetate/hexane).

Workup

  1. customThe ice bath was removed after 30 minutes
  2. customwas reduced in volume under vacuum at 25° C.
  3. customto give an oil
  4. washsuccessively washed with 1N hydrochloric acid (1×50 mL), saturated sodium bicarbonate (1×50 mL) and brine (1×50 mL)
  5. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  6. customevaporated under vacuum
  7. customto give crude product
  8. customThe crude product was purified by column chromatography on silica gel
  9. washeluting with 60:40 hexane

Sources & evidence

ORD record
ord-5a0f9c5e60e840cd959534164c8e3bd6
Source dataset
uspto-grants-2000_02
Patent number
US06025472

Reaction notes

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