Dimethylformamide → tert-butyl (2S)-2-(4-cyanophenyl)morpholine-4-carboxylate

HRID 710247Notes

Reaction equation

HRID 710247 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[CH:4][CH:3]=1.[CH3:21][N:22](C)C=O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C-]#N.[Zn+2].[C-]#N>[C:21]([C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[CH:4][CH:3]=1)#[N:22]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 58097875tert-butyl (2S)-2-(4-bromophenyl)morpholine-4-carboxylate

Product 1

HCID 66861409tert-butyl (2S)-2-(4-cyanophenyl)morpholine-4-carboxylateYield 69%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
85 °C

Procedure

A mixture of (S)-tert-butyl 2-(4-bromophenyl)morpholine-4-carboxylate (400 mg, 1.17 mmol), tetrakis(triphenylphosphine)palladium(0) (405 mg, 0.35 mmol) and zinc cyanide (206 mg, 1.75 mmol) in dimethylformamide (6 ml) was degassed with argon and heated in a closed tube at 85° C. on a Büchi shaker overnight. After cooling water (30 ml) was added, and the reaction mixture was extracted with ethyl acetate (50 ml). The aqueous phase was re-extracted with ethyl acetate (50 ml). The combined organic layers were re-extracted with conc. Sodium chloride solution, dried (MgSO4) and evaporated. The residue was purified by flash chromatography (20 g silica gel, 10% ethyl acetate in heptane) to yield a white solid (233 mg, 69%). MS (ISP): 289.1 ([M+H]+), 306.2 ([M+NH4]+).

Workup

  1. customwas degassed with argon
  2. temperatureAfter cooling water (30 ml)
  3. additionwas added
  4. extractionthe reaction mixture was extracted with ethyl acetate (50 ml)
  5. extractionThe aqueous phase was re-extracted with ethyl acetate (50 ml)
  6. extractionThe combined organic layers were re-extracted with conc. Sodium chloride solution
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe residue was purified by flash chromatography (20 g silica gel, 10% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-6aab78deb6fd45be876d214dd2156f5c
Source dataset
uspto-grants-2015_11
Patent number
US09181230B2

Reaction notes

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