4-Methylmorpholine → HCID 69286027, compound

HRID 2225271Notes

Reaction equation

HRID 2225271 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:4]=[C:5]([CH:13]=[CH:14][CH:15]=1)[C:6]([NH:8][CH2:9][C:10]([OH:12])=O)=[O:7].CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:33][C@H:34]1[CH2:39][CH2:38][C@@H:37]([N:40]([CH:42]([CH3:44])[CH3:43])[CH3:41])[CH2:36][C@H:35]1[CH2:45][OH:46]>C1COCC1.O>[OH:46][CH2:45][C@@H:35]1[CH2:36][C@H:37]([N:40]([CH:42]([CH3:43])[CH3:44])[CH3:41])[CH2:38][CH2:39][C@@H:34]1[NH:33][C:10](=[O:12])[CH2:9][NH:8][C:6](=[O:7])[C:5]1[CH:13]=[CH:14][CH:15]=[C:3]([C:2]([F:1])([F:17])[F:16])[CH:4]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2777432((3-(Trifluoromethyl)benzoyl)amino)acetic acidHCID 45098150HCID 45098150, compound

Product 1

HCID 69286027HCID 69286027, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (3-Trifluoromethyl-benzoylamino)-acetic acid (1.76 g, 0.0071 mol) in THF was cooled in an ice bath and treated with N-methylmorpholine(0.80 g, 0.0080 mol) and then drop-wise with isobutyl chloroformate (1.0 g, 0.007 mol). The resulting mixture was stirred for 5 min and then treated with a solution of ((1R,2S,5R)-2-amino-5-(isopropyl(methyl)amino)cyclohexyl)methanol (1.3 g, 0.0065 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 5-8% [NH4OH/MeOH]/CH2Cl2) to give 1.2 g of the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ(TMS): 8.15 (s, 1 H), 8.05 (d, J=7.8 Hz, 1 H), 7.76 (d, J=7.8 Hz, 1 H), 7.76 (bs, 1 H), 7.57 (t, J=7.8 Hz, 1 H), 7.17 (bs, 1 H), 4.26 (m, 1 H), 4.26 (dd, J=5 Hz, J=16 Hz, 1 H), 4.13 (dd, J=5 Hz, J=16 Hz, 1 H), 3.27 (m, 1 H), 3.17 (m, 1 H), 2.57 (m, 2 H), 2.24 (s, 3 H), 1.92-1.60 (m, 7 H), 1.05 (d, J=6.5 Hz, 6 H); MS found: (M+H)+=430.48.

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 5-8% [NH4OH/MeOH]/CH2Cl2)

Sources & evidence

ORD record
ord-ce1d708b8fc24264bfc162b34a373850
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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