Sodium Hydroxide → tert-Butyl {(1S)-1-[(2R)-oxiran-2-yl]-2-phenylethyl}carbamate

HRID 1884591Notes

Reaction equation

HRID 1884591 reaction equation
[OH-].[Na+].[C:3]([O:7][C:8]([NH:10][C@@H:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C@@H:12]([OH:15])[CH2:13]Cl)=[O:9])([CH3:6])([CH3:5])[CH3:4]>CC(O)C>[C:3]([O:7][C:8]([NH:10][C@@H:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C@H:12]1[O:15][CH2:13]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 99441391,1-Dimethylethyl N-[(1S,2R)-3-chloro-2-hydroxy-1-(phenylmethyl)propyl]carbamate

Product 1

HCID 9813904tert-Butyl {(1S)-1-[(2R)-oxiran-2-yl]-2-phenylethyl}carbamate

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

2-Propanol (12.9 ml) and aqueous 6.08 mol/l sodium hydroxide solution (2.94 g) were added to a solution containing (2R, 3S)-3-tert-butoxycarbonylamino-1-chloro-2-hydroxy-4-phenylbutane obtained in Example 17 {(2R, 3S) content of 2.79 g; (2S, 3S) content of 83.9 mg}, for agitation at 4° C. for 15 hours. The resulting solution was analyzed by HPLC, which indicates that the objective (2R, 3S) compound was at 94.0% (HPLC area ratio). After the reaction was quenched by the addition of aqueous 4.4% citric acid solution (20.9 g), the reaction solution was cooled from 25° C. to −10° C. over 2.3 hours; then, the seed crystal was added, followed by addition of water (19.2 ml) for overnight agitation, to crystallize (2R, 3S)-3-tert-butoxycarbonylamino-1,2-epoxy-4-phenylbutane. By filtration of the resulting slurry, the crystal of the objective (2R, 3S)-3-tert-butoxycarbonylamino-1,2-epoxy-4-phenylbutane was obtained {(2R, 3S) yield: 2.4 g (96.2%)}. The dried crystal was then analyzed by HPLC. (2R, 3S): (2S, 3S)=97.9:2.1. Additionally, the purity of (2R, 3S) was at 95.4% (HPLC area ratio).

Workup

  1. customAfter the reaction was quenched by the addition of aqueous 4.4% citric acid solution (20.9 g)
  2. temperaturethe reaction solution was cooled from 25° C. to −10° C. over 2.3 hours
  3. additionthen, the seed crystal was added
  4. additionfollowed by addition of water (19.2 ml) for overnight agitation
  5. customto crystallize (2R, 3S)-3-tert-butoxycarbonylamino-1,2-epoxy-4-phenylbutane
  6. filtrationBy filtration of the resulting slurry

Sources & evidence

ORD record
ord-80d850c461794f229cf62f3641e0941a
Source dataset
uspto-grants-2004_07
Patent number
US06765100B2

Reaction notes

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