Triethylamine → (S)-2-(Boc-amino)-3-cyclohexyl-N-methoxy-N-methylpropanamide

HRID 1078087

Reaction equation

HRID 1078087 reaction equation
[CH3:1][C:2]([CH3:19])([O:4][C:5]([NH:7][C@@H:8]([CH2:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:9]([OH:11])=O)=[O:6])[CH3:3].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH3:33][NH:34][O:35][CH3:36].C(N(CC)CC)C>O1CCCC1>[CH3:19][C:2]([CH3:1])([O:4][C:5]([NH:7][C@@H:8]([CH2:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:9]([N:34]([O:35][CH3:36])[CH3:33])=[O:11])=[O:6])[CH3:3]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 10588189(2S)-2-(((tert-butoxy)carbonyl)amino)-3-cyclohexylpropanoic acid

Product 1

HCID 10495486(S)-2-(Boc-amino)-3-cyclohexyl-N-methoxy-N-methylpropanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-α-[[(1,1-dimethylethoxy)carbonyl]amino]cyclohexanepropanoic acid (93 g., 343 mmole) in dry tetrahydrofuran (1 l.) was added a 20% molar excess of 1,1'-carbonyldiimidazole over a period of less than 10 minutes with very efficient stirring to keep the internal temperature below 30°. After stirring for 30 minutes, N,O-dimethylhydroxylamine hydrochloride (36.8 g., 377 mmole) was added, followed by triethylamine (38.2 g., 377 mmole). After stirring at room temperature for 4 hours, the reaction mixture was filtered and the resulting filtrate was concentrated in vacuo. The amber colored residue (100 g.) was dissolved in ether (900 ml.) and poured into 1N HCl (1 l.). The acidic aqueous phase was separated, further extracted with ether and the combined ethereal solutions were washed with water, saturated sodium bicarbonate, water, and brine, then dried (MgSO4) to give (S)-α-[[(1,1-dimethylethoxy)carbonyl]amino]-N-methoxy-N-methylcyclohexanepropanamide as a colorless oil. [α]D =-12.9° (c=1, methanol). TLC (silica gel; 1:1, ethyl acetate:hexanes) Rf =0.58.

Workup

  1. customthe internal temperature below 30°
  2. stirringAfter stirring for 30 minutes
  3. stirringAfter stirring at room temperature for 4 hours
  4. filtrationthe reaction mixture was filtered
  5. concentrationthe resulting filtrate was concentrated in vacuo
  6. dissolutionThe amber colored residue (100 g.) was dissolved in ether (900 ml.)
  7. additionpoured into 1N HCl (1 l.)
  8. customThe acidic aqueous phase was separated
  9. extractionfurther extracted with ether
  10. washthe combined ethereal solutions were washed with water, saturated sodium bicarbonate, water, and brine
  11. dry with materialdried (MgSO4)

Sources & evidence

ORD record
ord-456b397398dc412abd10e1cb63a2c6d4
Source dataset
uspto-grants-1996_08
Patent number
US05545838

Linked notes

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