Diisopropylethylamine → HCID 58303022, compound

HRID 587353Notes

Reaction equation

HRID 587353 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[CH2:13][N:12]([C:14]([CH:16]3[CH2:21][CH2:20][N:19]([C:22]([C:24]4([CH3:27])[CH2:26][CH2:25]4)=[O:23])[CH2:18][CH2:17]3)=[O:15])[CH2:11][C@@H:10]2[N:28]([CH3:32])[C:29](Cl)=[O:30])[CH:5]=[CH:6][C:7]=1[Cl:8].[CH:33]1([CH2:36][CH2:37][NH:38][CH3:39])[CH2:35][CH2:34]1.C(N(CC)C(C)C)(C)C>C1COCC1.C(OCC)(=O)C>[CH:33]1([CH2:36][CH2:37][N:38]([CH3:39])[C:29]([N:28]([C@@H:10]2[C@@H:9]([C:4]3[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=3)[CH2:13][N:12]([C:14]([CH:16]3[CH2:17][CH2:18][N:19]([C:22]([C:24]4([CH3:27])[CH2:25][CH2:26]4)=[O:23])[CH2:20][CH2:21]3)=[O:15])[CH2:11]2)[CH3:32])=[O:30])[CH2:35][CH2:34]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 54298868HCID 54298868, compoundHCID 87318749HCID 87318749, compound

Product 1

HCID 58303022HCID 58303022, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of rac-{(3R,4S)-4-(3,4-Dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-methyl-carbamic acid chloride (250 mg, 0.50 mmol) in THF (1 mL) was added (2-cyclopropyl-ethyl)-methyl-amine (99 mg, 1.0 mmol) and N,N-diisopropyl ethyl amine (256, 1.50 mmol). The solution was irradiated in the microwave for 900 sec. at 130° C. before it was diluted with ethyl acetate (15 mL) and washed with an aqueous solution of sodium carbonate (1 M, 15 mL). The organic layer was separated and washed with brine (15 mL) and the aqueous layers were extracted with ethyl acetate (20 mL). The combined organic layers were dried over sodium sulfate and concentrated. Purification by chromatography (SiO2,ethyl acetate:methanol=100:0 to 85:15) afforded the title compound (202 mg, 72%) as a white foam. MS m/e: 563.4 [M]+.

Workup

  1. customThe solution was irradiated in the microwave for 900 sec
  2. washwashed with an aqueous solution of sodium carbonate (1 M, 15 mL)
  3. customThe organic layer was separated
  4. washwashed with brine (15 mL)
  5. extractionthe aqueous layers were extracted with ethyl acetate (20 mL)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationconcentrated
  8. customPurification by chromatography (SiO2,ethyl acetate:methanol=100:0 to 85:15)

Sources & evidence

ORD record
ord-6a0ef5cb360d4061a74d1255d766a0c5
Source dataset
uspto-grants-2016_01
Patent number
US09226916B2

Reaction notes

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