Pyridine → HCID 19363745, compound

HRID 850378Notes

Reaction equation

HRID 850378 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:14][CH2:13][CH:12]([C:15]([C:28]3[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[CH:30][CH:29]=3)([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[OH:16])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.Cl[C:40]([O:42][CH3:43])=[O:41].N1C=CC=CC=1.[Cl-].[Na+]>O1CCCC1.C(OCC)(=O)C>[CH3:43][O:42][C:40]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:14][CH2:13][CH:12]([C:15]([C:28]3[CH:29]=[CH:30][C:31]([O:34][C:35]([F:38])([F:36])[F:37])=[CH:32][CH:33]=3)([C:17]3[CH:18]=[CH:19][C:20]([O:23][C:24]([F:25])([F:26])[F:27])=[CH:21][CH:22]=3)[OH:16])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1)=[O:41]

Participants

7

Reactant 4

HCID 1049PyridineHCID 5234Sodium ChlorideHCID 6586Methyl chloroformateHCID 19363752HCID 19363752, compound

Product 1

HCID 19363745HCID 19363745, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A stirred solution of 0.8 gram (0.0014 mole) of N-(4-aminophenylmethyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine in 15 mL of tetrahydrofuran was cooled to 0° C., and 0.11 mL of methyl chloroformate was added dropwise from a syringe. Upon completion of the addition, 0.12 mL of pyridine was added in one portion. The reaction mixture was allowed to warm to ambient temperature where it stirred for about 18 hours. After this time the reaction mixture was poured into a mixture of ethyl acetate and an aqueous solution saturated with sodium chloride. After a period of stirring, the organic layer was separated and dried with sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure to a residual solid. The solid was subjected to column chromatography on silica gel, with pure methylene chloride, and 1:9, 1:4, 1:3, and 3:7 mixtures of acetone:methylene chloride as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding 0.45 gram of N-[4-(methoxycarbonylamino)phenylmethyl]-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionwas added in one portion
  2. stirringAfter a period of stirring
  3. customthe organic layer was separated
  4. dry with materialdried with sodium sulfate
  5. filtrationThe mixture was filtered
  6. concentrationthe filtrate was concentrated under reduced pressure to a residual solid
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0948bd7b0b124ad88e02da34d9ed23c6
Source dataset
uspto-grants-2000_01
Patent number
US06017931

Reaction notes

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