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

HRID 632018Notes

Reaction equation

HRID 632018 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-7cb1764fd4fe4a40989c54f59a025917
Source dataset
uspto-grants-2016_04
Patent number
US09321727B2

Reaction notes

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