Triphenylphosphine → (2S)-2-[4-(hydroxymethyl)-2-oxo-1-pyrrolidinyl]-N-methylbutanamide

HRID 900309Notes

Reaction equation

HRID 900309 reaction equation
C[O:2][C:3]([CH:5]1[CH2:9][N:8]([C@@H:10]([CH2:14][CH3:15])[C:11]([NH2:13])=[O:12])[C:7](=[O:16])[CH2:6]1)=[O:4].[BH4-].[Na+].[NH4+].[Cl-].[CH:21]1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.I[CH2:41]C1CN([C@@H](CC)C(N)=O)C(=O)C1>CCO.C(Cl)Cl.CC(C)=O>[OH:2][CH2:3][CH:5]1[CH2:9][N:8]([C@@H:10]([CH3:14])[C:11]([NH2:13])=[O:12])[C:7](=[O:16])[CH2:6]1.[OH:4][CH2:3][CH:5]1[CH2:9][N:8]([C@@H:10]([CH2:14][CH2:15][CH3:21])[C:11]([NH2:13])=[O:12])[C:7](=[O:16])[CH2:6]1.[OH:2][CH2:3][CH:5]1[CH2:9][N:8]([C@@H:10]([CH2:14][CH3:15])[C:11]([NH:13][CH3:41])=[O:12])[C:7](=[O:16])[CH2:6]1

Participants

11

Reactant 5

HCID 11776TriphenylphosphineHCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 9922693(2S)-2-[4-(iodomethyl)-2-oxo-1-pyrrolidinyl]butanamideHCID 44367383(2S)-2-(4-methoxycarbonyl-2-oxo-1-pyrrolidinyl)butanamide

Product 3

HCID 66725930(2S)-2-[4-(hydroxymethyl)-2-oxo-1-pyrrolidinyl]-N-methylbutanamideHCID 66725938(2S)-2-[4-(hydroxymethyl)-2-oxo-1-pyrrolidinyl]pentanamideHCID 66725990(2S)-2-[4-(hydroxymethyl)-2-oxo-1-pyrrolidinyl]propanamide

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 702EthanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

In a 2 l three necked flask fitted with mechanical stirrer and reflux condenser, under inert atmosphere, a solution of 133 g (583 mmoles, 1 eq) of (2S)-2-(4-methoxycarbonyl-2-oxo-1-pyrrolidinyl)butanamide 11 in 200 ml of EtOH is added to 300 ml of EtOH, and the mixture cooled down to 0° C. 66.2 g (1.74 mole, 12 eq) of solid NaBH4 are then added by portions over 1.5 hour, all the while maintaining the temperature between 2 and 4° C. After 2 hours, the temperature is raised to 12° C. for 1 hour, and lowered again to 2-4° C. 240 ml of a saturated solution of NH4Cl are added dropwise over 1 hour, followed by 120 ml of acetone, and the mixture is left overnight at room temperature. The mixture is filtered, the precipitate washed with 3×70 ml of EtOH and the combined organic fractions concentrated to dryness to give 148 g of crude 6. It is suspended in 300 ml of CH2Cl2 and stirred for 30 min, filtered, washed with 2×100 ml of CH2Cl2 and dried to give 114 g of pure 6, 98%. Alternatively, (2S)-2-[4-(hydroxymethyl)-2-oxo-1-pyrrolidinyl]propanamide, (2S)-2-[4-(hydroxymethyl)-2-oxo-1-pyrrolidinyl]pentanamide, (2S)-2-[4-(hydroxymethyl)-2-oxo-1-pyrrolidinyl]-N-methylbutanamide are prepared in similar ways. 7.1. Synthesis by Direct Transformation of the Alcohol using PPh3 7.1.1. Synthesis of (2S)-2-[4-(iodomethyl)-2-oxo-1-pyrrolidinyl]butanamide 10

Workup

  1. temperaturereflux condenser
  2. temperatureall the while maintaining the temperature between 2 and 4° C
  3. temperaturethe temperature is raised to 12° C. for 1 hour
  4. customlowered again to 2-4° C
  5. waitthe mixture is left overnight at room temperature
  6. filtrationThe mixture is filtered
  7. washthe precipitate washed with 3×70 ml of EtOH
  8. concentrationthe combined organic fractions concentrated to dryness
  9. customto give 148 g of crude 6
  10. filtrationfiltered
  11. washwashed with 2×100 ml of CH2Cl2
  12. customdried
  13. customto give 114 g of pure 6, 98%

Sources & evidence

ORD record
ord-3dcc260ec9204f90bf9ad04f83d54101
Source dataset
uspto-grants-2008_04
Patent number
US07358276B2

Reaction notes

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