2,6-Dimethylmorpholine, cis- → (s)-{1-[3-(cis-2,6-Dimethylmorpholin-4-yl)phenyl]ethyl}-carbamic acid tert-butyl ester

HRID 2307443

Reaction equation

HRID 2307443 reaction equation
[C:1]([O:5][C:6](=[O:17])[NH:7][C@H:8]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12](Br)[CH:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2].[CH3:18][C@H:19]1[O:24][C@@H:23]([CH3:25])[CH2:22][NH:21][CH2:20]1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6](=[O:17])[NH:7][C@H:8]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([N:21]2[CH2:20][C@H:19]([CH3:18])[O:24][C@H:23]([CH3:25])[CH2:22]2)[CH:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6415002,6-Dimethylmorpholine, cis-HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 56971804(S)-N-Boc-1-(3-bromophenyl)ethylamine

Product 1

HCID 69866002(s)-{1-[3-(cis-2,6-Dimethylmorpholin-4-yl)phenyl]ethyl}-carbamic acid tert-butyl esterYield 38%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

A solution of (S)-[1-(3-bromophenyl)ethyl]carbamic acid tert-butyl ester (5 g, 16.7 mmol), cis-2,6-dimethylmorpholine (5.75 g, 3eq.), palladium acetate (5 mol %, 187 mg), 2-(di-t-butylphosphino) biphenyl (10 mol %, 498 mg), and sodium tert-butoxide (1.68 g, 1.05eq) in toluene (33 ml) was stirred at 80° C. for 1.5 hours. The solution was filtered through Celite Pad and washed with ethyl acetate. The filtrate was concentrated under vacuum and purified by flash chromatography with gradient of 20% ethyl acetate/hexane to 30% ethyl acetate/hexane over 20 minutes. The product was obtained as a yellow solid (2.12 g, 38% yield).

Workup

  1. filtrationThe solution was filtered through Celite Pad
  2. washwashed with ethyl acetate
  3. concentrationThe filtrate was concentrated under vacuum
  4. custompurified by flash chromatography with gradient of 20% ethyl acetate/hexane to 30% ethyl acetate/hexane over 20 minutes

Sources & evidence

ORD record
ord-923968d37417419fa28ce7ba51443ad7
Source dataset
uspto-grants-2004_12
Patent number
US06831080B2

Linked notes

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