Sodium Carbonate → rac-[(3R,4S)-4-(3,4-Dichloro-phenyl)-1-(1-propionyl-piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

HRID 587334Notes

Reaction equation

HRID 587334 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:33])[N:10]([C@@H:12]2[C@@H:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=3)[CH2:15][N:14]([C:25]([CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[O:26])[CH2:13]2)[CH3:11])=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[C:43](Cl)(=[O:46])[CH2:44][CH3:45].C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:33])[N:10]([C@@H:12]2[C@@H:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=3)[CH2:15][N:14]([C:25]([CH:27]3[CH2:32][CH2:31][N:30]([C:43](=[O:46])[CH2:44][CH3:45])[CH2:29][CH2:28]3)=[O:26])[CH2:13]2)[CH3:11])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 62324Propionyl chlorideHCID 81531DiisopropylethylamineHCID 58303080[(3R,4S)-4-(3,4-Dichloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

Product 1

HCID 58303148rac-[(3R,4S)-4-(3,4-Dichloro-phenyl)-1-(1-propionyl-piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl esterYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of rac-[(3R,4S)-4-(3,4-dichloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester (200 mg, 0.41 mmol) in THF (2 mL) was added N,N-diisopropyl ethyl amine (208 μl, 1.21 mmol). After stirring for a period of 5 min propionyl chloride (53 μl, 0.61 mmol) was added. After stirring for 3 h at ambient temperature the reaction mixture was treated with an aqueous solution of sodium carbonate (1 M, 10 mL). The organic layer was separated and washed with brine (10 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 80:20) afforded the title compound (88 mg, 40%) as a white solid. MS m/e: 550.3 [M]+.

Workup

  1. additionwas added
  2. customThe organic layer was separated
  3. washwashed with brine (10 mL)
  4. extractionthe aqueous layers were extracted with ethyl acetate (20 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. concentrationconcentrated
  7. customPurification by chromatography (SiO2, ethyl acetate:methanol=100:0 to 80:20)

Sources & evidence

ORD record
ord-2ed48627d4ed478c8171d129e72fed30
Source dataset
uspto-grants-2016_01
Patent number
US09226916B2

Reaction notes

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