Dimethylformamide → alphahydroxy-N-[1-methyl-4-(3-pyridinyl)butyl]benzeneacetamide

HRID 2232705Notes

Reaction equation

HRID 2232705 reaction equation
[CH:1]1(N=C=NC2CCCCC2)[CH2:6]CCC[CH2:2]1.[C:16]([OH:26])(=O)[C@@H:17]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[OH:18].O[N:28]1[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[N:30]=N1.[CH3:37]N(C)C=O>>[OH:18][CH:17]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[C:16]([NH:28][CH:32]([CH3:37])[CH2:33][CH2:34][CH2:35][C:36]1[CH:31]=[N:30][CH:2]=[CH:1][CH:6]=1)=[O:26]

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 10868DicyclohexylcarbodiimideHCID 11914(-)-Mandelic acidHCID 757711-Hydroxybenzotriazole

Product 1

HCID 13999762alphahydroxy-N-[1-methyl-4-(3-pyridinyl)butyl]benzeneacetamide

Conditions

Temperature
-10 °C

Procedure

A solution of 281.5 g of 1,3-dicyclohexylcarbodiimide in 400 ml of dimethylformamide was added to a stirred solution of 204 g of (R,S)-alpha-methyl-3-pyridinebutanamine, 198.4 g of (R)-mandelic acid and 209.75 g of 1-hydroxybenzotriazole in 1400 mL of dimethylformamide, maintained at -10° C. during the addition by intermittent cooling with a dry ice-acetone bath. After stirring at -5° for 4 hours, then at room temperature overnight the mixture was recooled to 0° C. for 2 hours. The precipitated solids were filtered and washed in turn with cold dimethylformamide (2×150 mL) and ethyl acetate (2×300 mL). This material, a mixture of 1,3-dicyclohexylurea (DCU) and the less soluble (R*,R)-mandelamide, was dispersed in 2L of 1N HCl and stirred at room temperature for 3 hours. The undissolved solids (DCU) were removed by filtration and were washed with 200 mL of dilute HCl and with water. The filtrate was basified and the resulting material was collected by filtration, washed with water and dried in vacuo to give 64.4 g of [R-(R*,R*)]-alpha-hydroxy-N-[1-methyl-4-(3-pyridinyl)butyl]benzeneacetamide, the (R*,R)-mandelamide, mp 144°-146° C.; [α]D25 -27.8° (c, 1.0, MeOH).

Workup

  1. temperatureby intermittent cooling with a dry ice-acetone bath
  2. waitat room temperature overnight the mixture was recooled to 0° C. for 2 hours
  3. filtrationThe precipitated solids were filtered
  4. washwashed in turn with cold dimethylformamide (2×150 mL) and ethyl acetate (2×300 mL)
  5. additionThis material, a mixture of 1,3-dicyclohexylurea (DCU)
  6. additionthe less soluble (R*,R)-mandelamide, was dispersed in 2L of 1N HCl
  7. stirringstirred at room temperature for 3 hours
  8. customThe undissolved solids (DCU) were removed by filtration
  9. washwere washed with 200 mL of dilute HCl and with water
  10. filtrationthe resulting material was collected by filtration
  11. washwashed with water
  12. customdried in vacuo

Sources & evidence

ORD record
ord-405655f72a8a415582fa9236ba25253b
Source dataset
uspto-grants-1988_11
Patent number
US04788206

Reaction notes

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