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Methanol → [(3S,4R)-1-(1-Acetyl-piperidine-4-carbonyl)-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

HRID 587398
Notes
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Reaction equation

HRID 587398 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:12][N:11]([C:13]([CH:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)=[O:14])[CH2:10][C@H:9]2[N:21]([CH3:32])[C:22](=[O:31])[O:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[C:42](Cl)(=[O:44])[CH3:43].CO>C(Cl)Cl>[F:30][C:27]1[CH:26]=[CH:25][C:24]([O:23][C:22](=[O:31])[N:21]([C@H:9]2[C@H:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[CH2:12][N:11]([C:13]([CH:15]3[CH2:20][CH2:19][N:18]([C:42](=[O:44])[CH3:43])[CH2:17][CH2:16]3)=[O:14])[CH2:10]2)[CH3:32])=[CH:29][CH:28]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 887MethanolHCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 58303156[(3S,4R)-4-(4-chloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

Product 1

HCID 58303121[(3S,4R)-1-(1-Acetyl-piperidine-4-carbonyl)-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester
Yield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 94 mg (0.204 mmol) 4-fluorophenyl (3S,4R)-4-(4-chlorophenyl)-1-(piperidine-4-carbonyl)pyrrolidin-3-yl(methyl)carbamate and 132 mg (1.02 mmol) DIPEA in 5 mL DCM was added 24.1 mg (0.3 mmol) acetyl chloride and stirred for 5 h. Methanol was added and stirred over night. The reaction mixture was extracted with sat NaHCO3 and the aqueous layer extracted with DCM. The combined organic layers were dried with Na2SO4, filtered off and concentrated in vacuum. The residue was subjected to purification by column chromatography on silica eluting with a gradient formed from DCM, methanol and NH3aq. The product containing fractions were evaporated to yield 53 mg (52%) of the title compound as light yellow foam. MS m/e: 502.2 [M+H]+.

Workup

  1. stirringstirred over night
  2. extractionThe reaction mixture was extracted with sat NaHCO3
  3. extractionthe aqueous layer extracted with DCM
  4. dry with materialThe combined organic layers were dried with Na2SO4
  5. filtrationfiltered off
  6. concentrationconcentrated in vacuum
  7. customThe residue was subjected to purification by column chromatography on silica eluting with a gradient
  8. customformed from DCM, methanol and NH3aq
  9. additionThe product containing fractions
  10. customwere evaporated

Sources & evidence

ORD record
ord-610707f4cd6b42ecadda7106063fbbda
Source dataset
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09226916B2

Reaction notes

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