Hydrochloric Acid → tert-Butyl 2-methyl-4-morpholino-4-oxobutan-2-ylcarbamate

HRID 927404Notes

Reaction equation

HRID 927404 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:15])([CH3:14])[CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[NH:47]1[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1.Cl>C(Cl)Cl>[CH3:14][C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])([CH2:10][C:11]([N:47]1[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1)=[O:13])[CH3:15]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 103760463-((tert-Butoxycarbonyl)amino)-3-methylbutanoic acid

Product 1

HCID 71105557tert-Butyl 2-methyl-4-morpholino-4-oxobutan-2-ylcarbamateYield 59.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-(tert-Butoxycarbonylamino)-3-methylbutanoic acid (2.7 g, 12.4 mmol), HBTU (CAN 94790-37-1, 6.1 g, 16.1 mmol) and triethylamine (CAN 121-44-8, 2.5 g, 24.8 mmol) was added to a solution of morpholine (CAN 110-91-8, 2.2 g, 24.8 mmol) in methylene chloride (50 mL). The mixture was stirred overnight at room temperature. Aqueous hydrochloride (1 N, 50 mL) was added, and the mixture extracted with methylene chloride. The organic extracts were washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (silica gel, 50 g, eluting with 30% ethyl acetate in petroleum ether) to give the product (2.1 g, 59%); MS (EI): m/e 287.1 [M+H]+.

Workup

  1. extractionthe mixture extracted with methylene chloride
  2. washThe organic extracts were washed with saturated aqueous sodium bicarbonate and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. custompurified by column chromatography (silica gel, 50 g, eluting with 30% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-719f2a5a19754d059967766313dec2f8
Source dataset
uspto-grants-2016_03
Patent number
US09290451B2

Reaction notes

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