Triethylamine → HCID 14836062, compound

HRID 1088545Notes

Reaction equation

HRID 1088545 reaction equation
CN(C)CCCN=C=NCC.[Br:12][C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[C:18]([O:27][CH3:28])[C:19]=2[C:23]([F:26])([F:25])[F:24])[C:14]=1[C:29]([OH:31])=O.ON1C2C=CC=CC=2N=N1.Cl.[NH:43]([CH2:45][C:46]([O:48][CH3:49])=[O:47])[CH3:44].C(N(CC)CC)C>CN(C=O)C.O>[Br:12][C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[C:18]([O:27][CH3:28])[C:19]=2[C:23]([F:25])([F:24])[F:26])[C:14]=1[C:29]([N:43]([CH3:44])[CH2:45][C:46]([O:48][CH3:49])=[O:47])=[O:31]

Participants

8

Reactant 5

HCID 8471Triethylamine2×HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 83544Glycine, N-methyl-, methyl ester, hydrochloride (1:1)HCID 15614957HCID 15614957, compound

Product 1

HCID 14836062HCID 14836062, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide (7.91 g, 1.2 eq) was added to a stirred solution of 2-bromo-6-methoxy-5-trifluoromethyl-1-naphthoic acid, prepared by the process of Example 14, Step 2 (12.00 g, 34.4 mmol) and 1-hydroxybenzotriazole (6.97 g, 1.5 eq) in anhydrous DMF (105 mL) at room temperature under a dry nitrogen atmosphere. Dissolution occurred after 20 minutes. After 1 hour, a suspension of methyl sarcosinate hydrochloride (9.56 g, 2.0 eq) in anhydrous DMF (60 mL) was added to the reaction mixture followed by triethylamine (15.8 mL, 3.3 eq). After 21/2 hours, more triethylamine (4.8 mL, 1.0 eq) was added. The reaction was diluted with water (1.6 L) after 181/2 hours. The aqueous phase was extracted with ether (4×250 mL). The extracts were combined and washed with 0.5N sodium hydroxide solution (1×200 mL) and saturated aqueous sodium chloride (1×200 mL). The ether phase was dried with magnesium sulfate and the ether was removed. The crude product was flash chromatographed (3:2 to 2:3 petroleum ether:ethyl acetate eluent gradient, silica) then reflash chromatographed (99:1 to 9:1 methylene chloride:acetonitrile eluent gradient, silica) to provide the product as a white foam (11.16 g, 75%).

Workup

  1. dissolutionDissolution
  2. waitAfter 1 hour
  3. additionwas added to the reaction mixture
  4. extractionThe aqueous phase was extracted with ether (4×250 mL)
  5. washwashed with 0.5N sodium hydroxide solution (1×200 mL) and saturated aqueous sodium chloride (1×200 mL)
  6. dry with materialThe ether phase was dried with magnesium sulfate
  7. customthe ether was removed
  8. customchromatographed (3:2 to 2:3 petroleum ether:ethyl acetate eluent gradient, silica)
  9. customthen reflash chromatographed (99:1 to 9:1 methylene chloride:acetonitrile eluent gradient, silica)

Sources & evidence

ORD record
ord-3f2678b975034cd18823265d330d33a6
Source dataset
uspto-grants-1990_10
Patent number
US04962224

Reaction notes

Loading…