Ethylmorpholine → HCID 11752641, compound

HRID 747883Notes

Reaction equation

HRID 747883 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([N:17]3[CH2:22][CH:21]([OH:23])[C:20]4[S:24][C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=5[C:19]=4[CH:18]3[C:31]([OH:33])=O)(=[O:16])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.ClC(OCC)=O.C(N1CCOCC1)C.C[Si](C)(C)[O:50][NH2:51]>C1COCC1>[OH:50][NH:51][C:31]([CH:18]1[C:19]2[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=3[S:24][C:20]=2[CH:21]([OH:23])[CH2:22][N:17]1[S:14]([C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[CH:9][CH:10]=1)(=[O:16])=[O:15])=[O:33]

Participants

6

Reactant 4

HCID 7525EthylmorpholineHCID 10928Ethyl chloroformateHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 69523397HCID 69523397, compound

Product 1

HCID 11752641HCID 11752641, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The carboxylic acid from step 3 (239 mg, 0.49 mmol) was dissolved in 4 ml of THF. After that, ethyl chloroformate (64 mg, 0.59 mmol) and N-ethylmorpholine (79.7 mg, 0.69 mmol) were added at 0° C. and preactivation was carried out at this temperature for one hour. O-Trimethylsilylhydroxylamine (208 mg, 1.98 mmol) was then added and the mixture was stirred overnight at from 0° C. to RT. The solvent was removed under reduced pressure and the residue was taken up in ethyl acetate; this solution was extracted by shaking with dilute HCl, water and sodium carbonate solution. The residue was dissolved, for direct preparative RP-HPLC, in a small quantity of a mixture of acetonitrile, water and 0.01% trifluoroacetic acid. Resulting fractions were pooled, acetonitrile was removed under reduced pressure and the remaining aqueous phase was freeze-dried. Yield: 4.5 mg; unreacted carboxylic acid and other, not specifically characterized, byproducts are obtained in addition. Analytical data are given in Table 1.

Workup

  1. customThe solvent was removed under reduced pressure
  2. extractionthis solution was extracted
  3. stirringby shaking with dilute HCl, water and sodium carbonate solution
  4. dissolutionThe residue was dissolved
  5. additionfor direct preparative RP-HPLC, in a small quantity of a mixture of acetonitrile, water and 0.01% trifluoroacetic acid
  6. customacetonitrile was removed under reduced pressure
  7. customthe remaining aqueous phase was freeze-dried
  8. custombyproducts are obtained in addition

Sources & evidence

ORD record
ord-05b5e1a0cd214a4d88d26fc111791206
Source dataset
uspto-grants-2008_07
Patent number
US07399770B2

Reaction notes

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