phenylalaninol, (S)- → rel-(1R,2R)-2-Methylcyclopropanecarboxylic acid

HRID 2422697Notes

Reaction equation

HRID 2422697 reaction equation
[CH3:1][C@@H:2]1[CH2:4][C@H:3]1[C:5]([OH:7])=[O:6].[NH2:8][C@@H:9]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:10][OH:11]>C(OCC)(=O)C>[CH3:1][C@@H:2]1[CH2:4][C@H:3]1[C:5]([OH:7])=[O:6].[NH2:8][C@@H:9]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:10][OH:11].[CH3:1][C@@H:2]1[CH2:4][C@H:3]1[C:5]([OH:7])=[O:6]

Participants

5

Reactant 2

HCID 447213phenylalaninol, (S)-2×HCID 6995705rel-(1R,2R)-2-Methylcyclopropanecarboxylic acid

Product 2

HCID 6995705rel-(1R,2R)-2-Methylcyclopropanecarboxylic acidHCID 67182208HCID 67182208, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
67.5 °C

Procedure

Racemic trans-2-methylcyclopropanecarboxylic acid (20 g, 0.2 mol) is dissolved in ethyl acetate (200 mL). (S)-2-Amino-3-phenyl-1-propanol [also known as (S)-phenylalaninol] (15.6 g, 0.103 mol, 0.51 equiv) is added in one portion, and the mixture heated to 65-70° C. After crystallization, which may be facilitated by seeding, the suspension is stirred at room temperature 20 h, then filtered; and the crystals are washed with ethyl acetate (2×15 mL). The crystals are dried at 40° C. under vacuum for 3 h: mass 18.4 g (37% molar yield, enantiomeric composition by chiral GC=85/15, chiral GC method below). The crystals are re-suspended in 370 mL ethyl acetate; the suspension is heated to reflux for 1 h, cooled to room temperature overnight, and the crystals filtered, washed and dried as above: mass 16.7 g (91% yield, chiral composition 96/4). A second purification in ethyl acetate (170 mL) as above affords (S)-2-amino-3-phenyl-1-propanol (R,R)-2-methylcyclopropanecarboxylic acid (1:1) salt (16.12 g, 96.5% yield, chiral composition 99/1=98% ee; 32% overall yield from racemic trans-2-methylcyclopropanecarboxylic acid).

Workup

  1. additionis added in one portion
  2. customAfter crystallization, which
  3. filtrationfiltered
  4. washand the crystals are washed with ethyl acetate (2×15 mL)
  5. customThe crystals are dried at 40° C. under vacuum for 3 h
  6. temperaturethe suspension is heated
  7. temperatureto reflux for 1 h
  8. temperaturecooled to room temperature overnight
  9. filtrationthe crystals filtered
  10. washwashed
  11. customdried as above: mass 16.7 g (91% yield, chiral composition 96/4)
  12. customA second purification in ethyl acetate (170 mL) as
  13. customabove affords

Sources & evidence

ORD record
ord-dacbf9d191f94a46b4e9ff7b9d74cfaa
Source dataset
uspto-grants-2011_06
Patent number
US07960419B2

Reaction notes

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