Diisopropylethylamine → (S)-tert-Butyl 4-(1-amino-3-(4-iodophenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216988Notes

Reaction equation

HRID 216988 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1([C:15]([OH:17])=O)[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:18][C@@H:19]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([I:30])=[CH:26][CH:25]=1)[C:20]([NH2:22])=[O:21].C(N(C(C)C)CC)(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CN(C)C=O>[NH2:22][C:20](=[O:21])[C@@H:19]([NH:18][C:15]([C:9]1([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:10][CH2:11][O:12][CH2:13][CH2:14]1)=[O:17])[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([I:30])=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 447705(S)-2-Amino-3-(4-iodophenyl)propanamideHCID 12682194-(Boc-amino)tetrahydropyran-4-carboxylic acid

Product 1

HCID 59568595(S)-tert-Butyl 4-(1-amino-3-(4-iodophenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
5 °C

Procedure

To a stirred suspension of 4-(tert-Butoxycarbonylamino)tetrahydro-2H-pyran-4-carboxylic acid, 20 g) in dimethylformamide was added (S)-2-amino-3-(4-iodophenyl)propanamide (Example 1, step (ii), 1.05 mol. eq.) and diisopropylethylamine (4 mol. eq.) at room temperature. The reaction mixture was cooled to 0-10° C. and stirred for 15 min. T3P (50% wt/wt in DMF; 1.7 mol. eq.) was added to the reaction mixture by dropwise addition at 0-10° C. over a period of 30 min and stirred for 1.5 h at the same temperature. The reaction mixture was quenched with water (2 rel. vol.) and stirred for 30 min at room temperature. 2-Methyltetrahydrofuran (15 rel. vol) and water (13 rel. vol) were added to the reaction mixture and extracted. The organic layer was separated and concentrated to 5 rel. vol. To the stirred organic portion was added toluene (10 rel. vol.) drop wise over a period of 30 min. The solution was stirred for 5 h at room temperature. The resulting solid material was filtered and washed with toluene (2 rel. vol), and dried the material at 50° C. under vacuum to afford the sub-titled compound (28.8 g).

Workup

  1. stirringstirred for 1.5 h at the same temperature
  2. customThe reaction mixture was quenched with water (2 rel. vol.)
  3. stirringstirred for 30 min at room temperature
  4. addition2-Methyltetrahydrofuran (15 rel. vol) and water (13 rel. vol) were added to the reaction mixture
  5. extractionextracted
  6. customThe organic layer was separated
  7. concentrationconcentrated to 5 rel
  8. additionvol. To the stirred organic portion was added toluene (10 rel
  9. waitvol.) drop wise over a period of 30 min
  10. stirringThe solution was stirred for 5 h at room temperature
  11. filtrationThe resulting solid material was filtered
  12. washwashed with toluene (2 rel. vol)
  13. customdried the material at 50° C. under vacuum

Sources & evidence

ORD record
ord-9d9d604c77184994ab85483b2c3752b5
Source dataset
uspto-grants-2012_06
Patent number
US08193239B2

Reaction notes

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