4-Methylmorpholine → HCID 66705936, compound

HRID 2276375Notes

Reaction equation

HRID 2276375 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9]2)=[CH:4][CH:3]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[Cl:49][C:50]1[CH:51]=[CH:52][C:53]([C:56](O)=[O:57])=[N:54][CH:55]=1>CN(C=O)C.C(OCC)(=O)C>[C:16]([O:15][C:13]([N:10]1[CH2:11][CH2:12][CH:8]([C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:56]([C:53]3[CH:52]=[CH:51][C:50]([Cl:49])=[CH:55][N:54]=3)=[O:57])=[CH:7][CH:6]=2)[CH2:9]1)=[O:14])([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27628725-Chloro-2-picolinic acidHCID 573650691,1-Dimethylethyl 3-(4-aminophenyl)-1-pyrrolidinecarboxylate

Product 1

HCID 66705936HCID 66705936, compoundYield 101.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred suspension of (RS)-tert-butyl 3-(4-aminophenyl)pyrrolidine-1-carboxylate (200 mg, CAS 908334-28-1) in DMF (10 ml) were added sequentially N-methylmorpholine (0.22 ml), TBTU (490 mg) and 5-chloro-2-pyridine carboxylic acid (180 mg) and the mixture was stirred at room temperature for 90 min. The mixture was then diluted with ethyl acetate and washed sequentially with 1 M aq. hydrochloric acid and with saturated brine. The phases were separated and the organic phase was dried over sodium sulphate and concentrated in vacuo. The residue was purified by column chromatography (SiO2; gradient: heptane/EtOAc) to give (RS)-3-{4-[(5-chloro-pyridine-2-carbonyl)-amino]-phenyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (310 mg, quant.) as a white solid. MS (ISP): 421.3 ([M+NH4]+), 419.2 ([M+NH4]+).

Workup

  1. washwashed sequentially with 1 M aq. hydrochloric acid and with saturated brine
  2. customThe phases were separated
  3. dry with materialthe organic phase was dried over sodium sulphate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (SiO2; gradient: heptane/EtOAc)

Sources & evidence

ORD record
ord-b7215dbfc650433fa5786e72182c9ff8
Source dataset
uspto-grants-2015_09
Patent number
US09132136B2

Reaction notes

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