4-Methylmorpholine → HCID 86596968, compound

HRID 2225291Notes

Reaction equation

HRID 2225291 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([OH:8])=O.CN1CCOCC1.ClC(OCC(C)C)=O.C(OC([NH:39][CH2:40][C:41]([NH:43][C@H:44]1[CH2:49][CH2:48][C@@H:47]([N:50]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH:51]([CH3:53])[CH3:52])[CH2:46][C@H:45]1[C:61]([O:63][CH:64]([CH3:66])[CH3:65])=[O:62])=[O:42])=O)C1C=CC=CC=1>C1COCC1.O>[C:57]([O:56][C:54]([N:50]([CH:51]([CH3:53])[CH3:52])[C@H:47]1[CH2:46][C@@H:45]([C:61]([O:63][CH:64]([CH3:66])[CH3:65])=[O:62])[C@@H:44]([NH:43][C:41](=[O:42])[CH2:40][NH:39][C:6](=[O:8])[C:5]2[CH:9]=[CH:10][CH:11]=[C:3]([C:2]([F:1])([F:13])[F:12])[CH:4]=2)[CH2:49][CH2:48]1)=[O:55])([CH3:59])([CH3:58])[CH3:60]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 99633-(Trifluoromethyl)benzoic acidHCID 62365Isobutyl chloroformateHCID 86596969HCID 86596969, compound

Product 1

HCID 86596968HCID 86596968, compoundYield 63.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3-Trifluoromethyl-benzoic acid (0.23 g, 0.0012 mol) in THF was cooled in an ice bath and treated with N-methylmorpholine(0.13 g, 0.0013 mol) and then drop-wise with isobutyl chloroformate (0.16 g, 0.0012 mol). The resulting mixture was stirred for 5 min and then treated with a solution of isopropyl (1R,2S,5R)-2-(2-aminoacetamido)-5-(tert-butoxycarbonyl-isopropyl-amino)cyclohexanecarboxylate (0.45 g, 0.0011 mol; See Example 8b, Step 4) in THF. The resulting mixture was stirred for 30 minutes and then diluted with water and extracted into CH2Cl2. The extract was washed with dilute NaOH, water, and brine and then concentrated under vacuum. The residue was chromatographed on silica gel (elution 55% ethyl acetate/hexane) to give 0.4 g of isopropyl(1R,2S,5R)-5-(tert-butoxycarbonyl-isopropyl-amino)-2-(2-(3-trifluoromethyl-benzamido)acetamido)cyclohexanecarboxylate as a white solid, MS found: (M+H)+=572.4.

Workup

  1. stirringThe resulting mixture was stirred for 30 minutes
  2. extractionextracted into CH2Cl2
  3. washThe extract was washed with dilute NaOH, water, and brine
  4. concentrationconcentrated under vacuum
  5. customThe residue was chromatographed on silica gel (elution 55% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-a1207922d07143f6a8a6321caa99fd22
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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