4-Methylmorpholine → HCID 69285460, compound

HRID 2225273Notes

Reaction equation

HRID 2225273 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.[NH2:29][CH2:30][C:31]([NH:33][C@H:34]1[CH2:39][CH2:38][C@@H:37]([N:40]([CH:48]([CH3:50])[CH3:49])[C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[CH2:36][C@H:35]1[CH2:51][OH:52])=[O:32]>C1COCC1.O>[OH:52][CH2:51][C@H:35]1[C@@H:34]([NH:33][C:31](=[O:32])[CH2:30][NH:29][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)[CH2:39][CH2:38][C@@H:37]([N:40]([CH:48]([CH3:50])[CH3:49])[C:41](=[O:47])[O:42][C:43]([CH3:44])([CH3:45])[CH3:46])[CH2:36]1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 99633-(Trifluoromethyl)benzoic acidHCID 62365Isobutyl chloroformateHCID 69286047HCID 69286047, compound

Product 1

HCID 69285460HCID 69285460, compoundYield 93.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3-Trifluoromethyl-benzoic acid (0.55 g, 0.0029 mol) in THF was cooled in an ice bath and treated with N-methylmorpholine (0.3 g, 0.003 mol) and then drop-wise with isobutyl chloroformate (0.39 g, 0.0029 mol). The resulting mixture was stirred for 5 min and then treated with a solution of tert-butyl(1R,3R,4S)-4-(2-aminoacetamido)-3-(hydroxymethyl)cyclohexyl-(isopropyl)carbamate (2.8 g, 0.01 mol) 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, then 100% ethyl acetate) to give 1.4 g of tert-butyl(1R,3R,4S)-3-(hydroxymethyl)-4-(2-(3-(trifluoromethyl)-benzamido)acetamido)cyclohexyl(isopropyl)carbamate as a white solid. MS found: (M+H)+=516.3.

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 (
  6. washelution 55% ethyl acetate/hexane

Sources & evidence

ORD record
ord-a20a20362585438b8ff25d608e091220
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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