1,2-Dichloroethane → tert-butyl (2S)-2-(2-(4-fluorophenethyl)-5-[1-(thiazol-2-yl)-2-(1-methylimidazol-5-yl)ethoxymethyl]benzoylamino}-4-methylsulfanylbutyrate

HRID 1251933Notes

Reaction equation

HRID 1251933 reaction equation
[F:1][C:2]1[CH:33]=[CH:32][C:5]([CH2:6][CH2:7][C:8]2[CH:16]=[CH:15][C:14]([CH:17]([O:23][CH2:24][CH2:25][C:26]3[N:30]([CH3:31])[CH:29]=[N:28][CH:27]=3)[C:18]3[S:19][CH:20]=[CH:21][N:22]=3)=[CH:13][C:9]=2[C:10](O)=[O:11])=[CH:4][CH:3]=1.Cl.[C:35]([O:39][C:40](=[O:47])[C@H:41]([CH2:43][CH2:44][S:45][CH3:46])[NH2:42])([CH3:38])([CH3:37])[CH3:36].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.Cl>CN(C1C=CN=CC=1)C.CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH2:7][C:8]2[CH:16]=[CH:15][C:14]([CH:17]([O:23][CH2:24][CH2:25][C:26]3[N:30]([CH3:31])[CH:29]=[N:28][CH:27]=3)[C:18]3[S:19][CH:20]=[CH:21][N:22]=3)=[CH:13][C:9]=2[C:10]([NH:42][C@@H:41]([CH2:43][CH2:44][S:45][CH3:46])[C:40]([O:39][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:47])=[O:11])=[CH:32][CH:33]=1

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 13141795h-Met-otbu.hclHCID 183243962-(4-Fluorophenethyl)-5-[1-(thiazol-2-yl)-2-(1-methylimidazol-5-yl)ethoxymethyl]benzoic acid

Product 1

HCID 57014961tert-butyl (2S)-2-(2-(4-fluorophenethyl)-5-[1-(thiazol-2-yl)-2-(1-methylimidazol-5-yl)ethoxymethyl]benzoylamino}-4-methylsulfanylbutyrate

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-(4-fluorophenethyl)-5-[1-(thiazol-2-yl)-2-(1-methylimidazol-5-yl)ethoxymethyl]benzoic acid (0.47 g, 1.06 mmol) (from Example 63), DMAP (0.62 g, 5.05 mmol), L-methionine tert-butyl ester HCl (0.62 g, 3.02 mmol), EDC (0.39 g, 2.02 mmol) and HOBT (0.137 g, 1.01 mmol) in DMF (25 ml) was stirred at ambient temperature under a nitrogen atmosphere for 16 hours. The reaction was evaporated to dryness and washed with aqueous citric acid (1M, 10 ml) and extracted with dichloromethane (20 ml). The extracts were washed with saturated brine, dried and filtered. Purification by flash column chromatography eluting with dichloromethanel methanol (95:5, 9:1 and 85:15) gave a gum. This was dissolved in ethyl acetate and treated with 1M ethereal HCl (10 ml). The resulting solid precipitate was isolated by centrifuging, further washing with diethyl ether and drying under high vacuum to give tert-butyl (2S)-2- (2-(4-fluorophenethyl)-5-[1-(thiazol-2-yl)-2-(1 -methylimidazol-5-yl)ethoxymethyl]benzoylamino}-4-methylsulfanylbutyrate as a white solid, (0.366 g, 55%).

Workup

  1. customThe reaction was evaporated to dryness
  2. washwashed with aqueous citric acid (1M, 10 ml)
  3. extractionextracted with dichloromethane (20 ml)
  4. washThe extracts were washed with saturated brine
  5. customdried
  6. filtrationfiltered
  7. customPurification by flash column chromatography
  8. washeluting with dichloromethanel methanol (95:5, 9:1 and 85:15)
  9. customgave a gum
  10. customThe resulting solid precipitate was isolated by centrifuging
  11. washfurther washing with diethyl ether
  12. customdrying under high vacuum

Sources & evidence

ORD record
ord-330a6c27ab794a17af44f6d93711714d
Source dataset
uspto-grants-2002_01
Patent number
US06342765B1

Reaction notes

Loading…