4-Methylmorpholine → [2-(Methoxymethyl-carbamoyl)-ethyl]-carbamic acid tert-butyl ester

HRID 1837888Notes

Reaction equation

HRID 1837888 reaction equation
[C:1]([NH:8][CH2:9][CH2:10][C:11]([OH:13])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN([P+](ON1N=[N:32][C:27]2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.CN1CC[O:45][CH2:44]C1>C(#N)C.CCOC(C)=O>[C:4]([O:3][C:1](=[O:2])[NH:8][CH2:9][CH2:10][C:11](=[O:13])[NH:32][CH2:27][O:45][CH3:44])([CH3:5])([CH3:6])[CH3:7]

Participants

6

Reactant 3

HCID 79724-MethylmorpholineHCID 76809N-((1,1-dimethylethoxy)carbonyl)-beta-alanineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate

Product 1

HCID 86584230[2-(Methoxymethyl-carbamoyl)-ethyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of BOC-beta-alanine (20 g, 105 mmol), 10-2 (10.3 g, 105 mmol), BOP reagent (46.5 g, 105 mmol), and N-methylmorpholine (46 mL, 420 mmol) in acetonitrile (500 mL) was stirred for 15 h. The reaction was diluted with EtOAc, washed with H2O, 10% KHSO4(aq.), sat. NaHCO3, dried (MgSO4) and concentrated to give crude [2-(methoxymethyl-carbamoyl)-ethyl]-carbamic acid tert-butyl ester 10-3 as a yellow oil. TLC Rf=0.42 (silica, 20% EtOAc/hexanes). To a solution of this crude amide in THF (500 mL) at 0° C. was added CH3MgBr (100 mL of 3M in ether, 300 mmol) over 30 minutes. After 2 h, 10% KHSO4(aq.) was added, the mixture warmed to 25° C., and diluted with EtOAc. The organics were washed with sat. NaHCO3, dried (MgSO4) and concentrated. Flash chromatography (silica, 20% EtOAc/hexanes) gave 10-4 as a yellow oil.

Workup

  1. washwashed with H2O, 10% KHSO4(aq.), sat. NaHCO3
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-f13996a8bcad45a3b4051e2cd7c5b3b8
Source dataset
uspto-grants-2004_08
Patent number
US06784190B2

Reaction notes

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