Heptane → (2S,3S,5R)-2-(3,5-difluorophenyl)-2-hydroxy-3,5-dimethylmorpholine-4-carboxylic acid chloromethyl ester

HRID 2357757Notes

Reaction equation

HRID 2357757 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@:9]2([OH:17])[O:14][CH2:13][C@@H:12]([CH3:15])[NH:11][C@H:10]2[CH3:16])[CH:5]=[C:6]([F:8])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].Cl[C:25]([O:27][CH2:28][Cl:29])=[O:26].CCCCCCC>ClCCl.O.C(OCC)(=O)C>[Cl:29][CH2:28][O:27][C:25]([N:11]1[C@H:12]([CH3:15])[CH2:13][O:14][C@:9]([C:4]2[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=2)([OH:17])[C@@H:10]1[CH3:16])=[O:26]

Participants

8

Reactant 4

HCID 8900HeptaneHCID 11430Potassium CarbonateHCID 60829ManifaxineHCID 62754Chloromethyl chloroformate

Product 1

HCID 59613210(2S,3S,5R)-2-(3,5-difluorophenyl)-2-hydroxy-3,5-dimethylmorpholine-4-carboxylic acid chloromethyl esterYield 81.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

To a stirring solution of (2S,3S,5R)-2-(3,5-difluorophenyl)-2-hydroxy-3,5-dimethylmorpholine (2.5 g, 10.28 mmol) in dichloromethane (50 mL) at room temperature under nitrogen, was added potassium carbonate (1.42 gm, 10.28 mmol). The mixture was cooled to 5° C. with a wet ice bath, and chloromethyl chloroformate (0.915 mL, 10.28 mmol) in dichloromethane (10 mL) was added dropwise. The mixture was allowed to warn to room temperature slowly and stirred over night. TLC analysis (1:1 heptane:ethyl acetate) indicated that the starting material was consumed and a new less polar spot had formed. Water was added to the mixture and then it was extracted with dichloromethane (3×). The organic layers were combined and dried over magnesium sulfate, filtered and the solvent was removed to afford a crude weight of 2.8 grams of (2S,3S,5R)-2-(3,5-difluorophenyl)-2-hydroxy-3,5-dimethylmorpholine-4-carboxylic acid chloromethyl ester (1410) as an opaque tar.

Workup

  1. customto warn to room temperature
  2. customwas consumed
  3. customa new less polar spot had formed
  4. extractionit was extracted with dichloromethane (3×)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent was removed

Sources & evidence

ORD record
ord-cfe0b918e9f8444ca14fdbe71722c72c
Source dataset
uspto-grants-2010_07
Patent number
US07763612B2

Reaction notes

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