Tetrahydrofuran → HCID 58912430, compound

HRID 47710Notes

Reaction equation

HRID 47710 reaction equation
[CH2:1]([C@@H:8]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[C:9](N(OC)C)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CCC[CH2:24]1>>[CH2:1]([C@@H:8]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:19])([CH3:20])[CH3:21])[C:9](=[O:10])[CH3:24])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 14131470Nalpha-(tert-Butoxycarbonyl)-N-methoxy-N-methyl-D-phenylalaninamide

Product 1

HCID 58912430HCID 58912430, compound

Conditions

Temperature
0 °C

Procedure

A mixture of 26.7 9 of tert-butyl (1R)-1-benzyl-2-[methoxy(methyl)amino]-2-oxoethylcarbamate in 534 cm3 of tetrahydrofuran dried over 4 Å sieves is cooled, under an inert atmosphere, to a temperature in the region of 0° C. 87 cm3 of a 3 M solution of methylmagnesium bromide in diethyl ether are then added over 45 minutes and the resulting mixture is then stirred for 1 hour at 0° C. and for 18 hours at room temperature. The reaction medium is re-cooled to a temperature in the region of 0° C., 55 cm3 of 1N hydrochloric acid are then added dropwise and the mixture is stirred for 30 minutes at this temperature. After filtration through Celite, 200 cm3 of water are added to the filtrate, which is then extracted with twice 200 cm3 of ethyl acetate. The combined organic phases are dried over sodium sulfate, filtered and then concentrated under reduced pressure (2 kPa) at a temperature in the region of 40° C. 21.2 g of tert-butyl (1R)-1-benzyl-2-oxopropylcarbamate are obtained in the form of yellow crystals melting at 59° C. 1H NMR spectrum (300 MHz, (CD3)2SO-d6, δ in ppm): 1.34 (s: 9H); 2.13 (s: 3H); 2.71 (dd, J=14 and 10 Hz: 1H); 3.01 (dd, J=14 and 5 Hz: 1H); 4.13 (mt: 1H); from 7.10 to 7.35 (mt: 6H).

Workup

  1. customdried over 4 Å sieves
  2. addition87 cm3 of a 3 M solution of methylmagnesium bromide in diethyl ether are then added over 45 minutes
  3. temperatureThe reaction medium is re-cooled to a temperature in the region of 0° C., 55 cm3 of 1N hydrochloric acid
  4. additionare then added dropwise
  5. stirringthe mixture is stirred for 30 minutes at this temperature
  6. filtrationAfter filtration through Celite, 200 cm3 of water
  7. additionare added to the filtrate, which
  8. extractionis then extracted with twice 200 cm3 of ethyl acetate
  9. dry with materialThe combined organic phases are dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-8ee2054673d6422a801b5dabc1e6ea58
Source dataset
uspto-grants-2004_03
Patent number
US06699895B2

Reaction notes

Loading…