Methylamine → HCID 57544617, compound

HRID 2355450Notes

Reaction equation

HRID 2355450 reaction equation
C1CC[CH:4]([N:7]=C=NC2CCCCC2)CC1.[NH:16]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@H:17]([C:20]([OH:22])=O)[CH2:18][OH:19].CN.[C:32]([O:35]C(=O)C)(=O)[CH3:33]>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCOCC>[C:32]([O:19][CH2:18][C@H:17]([NH:16][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:20]([NH:7][CH3:4])=[O:22])(=[O:35])[CH3:33]

Participants

8

Reactant 4

HCID 6329MethylamineHCID 7918Acetic AnhydrideHCID 10868DicyclohexylcarbodiimideHCID 98766N-[tert-butoxycarbonyl]-L-serine

Product 1

HCID 57544617HCID 57544617, compoundYield 78.4%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A three-neck, 3 L flask was dried under N2, cooled, equipped with an overhead stirrer and charged with a solution of DCC (20.6 g, 0.1 mol) in CH2Cl2 (0.65 L). This was cooled to 0° C. and solid Boc-Ser-OH (20.06 g, 0.1 mole) was added in one portion. This mixture was stirred for 5 min. Methylamine (33% w/w solution in EtOH, 12.5 mL, 0.1 mol) was added dropwise over 10 min maintaining the internal temperature below 8° C. The reaction was stirred for an additional 10 min, the cooling bath was emptied, and the reaction was stirred for 12 h; LC-MS (3 min) tR=0.75 min, m/z 241 (M+Na) indicated full conversion. DMAP (1.0 g, 0.008 mol) then acetic anhydride (105.0 mL, 1.1 mol) were added using an external water bath to moderate the exotherm (internal temp<30° C.). The reaction was stirred for 60 min. Celite (25 g) and Et2O (1 L) were added, the mixture was cooled to 0° C. and filtered through a pad of Celite and then a pad of SiO2. The filtrate was evaporated under reduced pressure. The resulting oil was chased with toluene (3×100 mL) and separated by chromatography on a SiO2 column to yield (2S)-3-acetoxy-2-(t-butoxycarbonylamino)-N-methylpropanamide (20.4 g, 78%). LC-MS (3 min) tR=0.75 min, m/z, 283 (M+Na).

Workup

  1. customA three-neck, 3 L flask was dried under N2
  2. temperaturecooled
  3. customequipped with an overhead stirrer
  4. temperaturemaintaining the internal temperature below 8° C
  5. stirringThe reaction was stirred for an additional 10 min
  6. stirringthe reaction was stirred for 12 h
  7. customLC-MS (3 min) tR=0.75 min, m/z 241 (M+Na)
  8. customthe exotherm (internal temp<30° C.)
  9. stirringThe reaction was stirred for 60 min
  10. temperaturethe mixture was cooled to 0° C.
  11. filtrationfiltered through a pad of Celite
  12. customThe filtrate was evaporated under reduced pressure
  13. customseparated by chromatography on a SiO2 column

Sources & evidence

ORD record
ord-98e99db976a2408bba7d60fdefa987ab
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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