Methanol → HCID 131720894, compound

HRID 400052Notes

Reaction equation

HRID 400052 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:13][CH2:14][OH:15])[CH2:12][CH2:11][NH:10][CH2:9]2)=[CH:4][CH:3]=1.[C:16]([C@:26]([C:43]([OH:45])=[O:44])([OH:42])[C@:27]([C:32](=[O:41])[C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=1)([OH:31])[C:28]([OH:30])=[O:29])(=[O:25])[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1.CO>CC(=O)CC>[C:32]([C@:27]([C:28]([OH:30])=[O:29])([OH:31])[C@:26]([C:16](=[O:25])[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1)([OH:42])[C:43]([OH:45])=[O:44])(=[O:41])[C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=1.[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:13][CH2:14][OH:15])[CH2:12][CH2:11][NH:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 887Methanol2×HCID 18464542HCID 18464542, compoundHCID 66875417(R, R)-di-p-anisoyltartaric acid

Product 1

HCID 131720894HCID 131720894, compound

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent3×

Procedure

Combine 2-[3-(4-fluoro-phenyl)-pyrrolidin-3-yl]-ethanol (32 mmol) and butanone (400 mL). Add a solution of (R,R)-di-p-anisoyltartaric acid (32 mmol) in butanone (80 mL). Heat to reflux. After 15 minutes, cool to ambient temperature and evaporate in vacuo to give a residue. Combine the residue and butanone (1000 mL) and methanol (430 mL) and heat. Add methanol (about 100 mL). Slowly cool to ambient temperature to give a solid. After 18 hours, filter the solid. Recrystallize the solid from butanone/methanol (80 mL/80 mL) to give (-)-2-[3-(4-fluoro-phenyl)-pyrrolidin-3-yl]-ethanol (R,R)-di-p-anisoyltartaric acid salt. [α]2D0 =-98.9 (c=0.70, methanol). Analysis on HPLC, on an analytical sample of the 3,4,5-trimethoxy-benzamide derivative, using a CHIRALPAK AD 25 cm×0.46 cm column eluting with pentane/ethanol/methanol/triethylamine (80/15/10/0.1) with a flow rate of 1.0 mL/minute indicates an enantiomeric excess of 99.6%, (99.6% ee), the 3,4,5-trimethoxy-benzamide prepared from (-)-2-[3-(4-fluoro-phenyl)-pyrrolidin-3-yl]-ethanol (R,R)-di-p-anisoyltartaric acid salt gave a retention time of 23.0 minutes, the 3,4,5-trimethoxy-benzamide prepared from (+)-2-[3-(4-fluoro-phenyl)-pyrrolidin-3-yl]-ethanol (R,R)-di-p-anisoyltartaric acid salt gave a retention time of 15.4 minutes.

Workup

  1. temperatureHeat to reflux
  2. customevaporate in vacuo
  3. customto give a residue
  4. temperatureheat
  5. temperatureSlowly cool to ambient temperature
  6. customto give a solid
  7. waitAfter 18 hours
  8. filtrationfilter the solid
  9. customRecrystallize the solid from butanone/methanol (80 mL/80 mL)

Sources & evidence

ORD record
ord-82078dc2cee248a9a5d188191fd84e31
Source dataset
uspto-grants-1998_10
Patent number
US05824690

Reaction notes

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