Tert-Butylamine → HCID 21074848, compound

HRID 1171578Notes

Reaction equation

HRID 1171578 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][CH2:15][N:14]([C@H:17]2[CH2:22][CH2:21][C:20](=O)[CH2:19][C@H:18]2[C:24]([O:26][CH3:27])=[O:25])[C:13]1=[O:28])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:29]([NH2:33])([CH3:32])([CH3:31])[CH3:30].[BH4-].[Na+].C([O-])(O)=O.[Na+]>CS(C)=O.CO>[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][CH2:15][N:14]([C@H:17]2[CH2:22][CH2:21][C@@H:20]([NH:33][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:19][C@H:18]2[C:24]([O:26][CH3:27])=[O:25])[C:13]1=[O:28])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6385Tert-ButylamineHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 68766738HCID 68766738, compound

Product 1

HCID 21074848HCID 21074848, compoundYield 84.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Procedure

A solution of (1R,2S)-methyl 2-((S)-3-(benzyloxy-carbonylamino)-2-oxopyrrolidin-1-yl)-5-oxocyclo-hexanecarboxylate (3.1 g, 8 mmol) in DMSO (7 ml) was treated with t-butylamine (1.75 g, 24 mol) and stirred for 10 minutes before Ti(i-OPr)4 (6.8 g, 24 mol) was added and the resulting mixture was stirred at room temperature for 2.5 h. Then NaBH4 (0.3 g, 8 mol) was added and stirred for 1.5 h before diluting slowly with methanol (gas evolution) and the resulting solution stirred an additional 1 h. While stirring vigorously, a sat'd solution of NaHCO3 was added, and the resulting suspension was filtered through Celite. The filter cake was washed thoroughly with CH2Cl2 several times and the combined washes were transferred to a separatory funnel. The organic layer was separated and washed with water and brine, concentrated and the residue chromatographed on silica gel (5% MeOH/CH2Cl2-8% NH4OH/MeOH/CH2Cl2) to give 3.0 g (80%) of (1R,2S,5R)-methyl 2-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexane-carboxylate. MS found: (M+H)+=446.30. Also obtained was 400 mg of the isomeric (1R,2S,5S)-methyl 2-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexanecarboxylate. MS found: (M+H)+=446.3.

Workup

  1. additionwas added
  2. stirringstirred for 1.5 h
  3. stirringthe resulting solution stirred an additional 1 h
  4. stirringWhile stirring vigorously
  5. filtrationthe resulting suspension was filtered through Celite
  6. washThe filter cake was washed thoroughly with CH2Cl2 several times
  7. customthe combined washes were transferred to a separatory funnel
  8. customThe organic layer was separated
  9. washwashed with water and brine
  10. concentrationconcentrated
  11. customthe residue chromatographed on silica gel (5% MeOH/CH2Cl2-8% NH4OH/MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ffa0917ef51a45fca04618203661e3ff
Source dataset
uspto-grants-2010_11
Patent number
US07829571B2

Reaction notes

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