Triethylamine → (S)-{1-[3-(2-methyl-morpholin-4-yl)-phenyl]-ethyl}-carbamic acid tert-butyl ester

HRID 2307445Notes

Reaction equation

HRID 2307445 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].Cl.[CH3:19][CH:20]1[O:25][CH2:24][CH2:23][NH:22][CH2:21]1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.C(N(CC)CC)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:22]2[CH2:23][CH2:24][O:25][CH:20]([CH3:19])[CH2:21]2)[CH:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 226055572-Methylmorpholine--hydrogen chloride (1/1)HCID 23676156Sodium t-butoxideHCID 56971804(S)-N-Boc-1-(3-bromophenyl)ethylamine

Product 1

HCID 69870688(S)-{1-[3-(2-methyl-morpholin-4-yl)-phenyl]-ethyl}-carbamic acid tert-butyl esterYield 58.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

The solution of (S)-[1-(3-bromo-phenyl)-ethyl]-carbamic acid tert-butyl ester (4.36 g, 14.5 mmol), 2-Methyl-morpholine hydrochloric acid salt (4 g. 2eq.), palladium acetate (20 mol %, 652 mg), 2-(di-t-butylphosphino) biphenyl (40 mol %, 1.73 g), triethylamine (4.45 ml, 2.2eq.), and sodium tert-butoxide (1.54 g, 1.1eq) in toluene (26 ml) was stirred at 80° C. for 2 days. The solution was filtered through Celite Pad and washed with ethyl acetate. The filtrate was washed with saturated sodium bicarbonate solution and the organic layer was separated. The aqueous layer was extracted with ethyl acetate three times. The combined organic layer was dried over magnesium sulfate and concentrated under vacuum. The crude product was purified by flash chromatography with 25% ethyl acetate/hexane. Yellow sticky oil was obtained as the product (2.7 g, 58% yield).

Workup

  1. filtrationThe solution was filtered through Celite Pad
  2. washwashed with ethyl acetate
  3. washThe filtrate was washed with saturated sodium bicarbonate solution
  4. customthe organic layer was separated
  5. extractionThe aqueous layer was extracted with ethyl acetate three times
  6. dry with materialThe combined organic layer was dried over magnesium sulfate
  7. concentrationconcentrated under vacuum
  8. customThe crude product was purified by flash chromatography with 25% ethyl acetate/hexane

Sources & evidence

ORD record
ord-ae41d9ff6a004657b43ae8a342feffbf
Source dataset
uspto-grants-2004_12
Patent number
US06831080B2

Reaction notes

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