Dimethylformamide → HCID 57973796, compound

HRID 1863920Notes

Reaction equation

HRID 1863920 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])[CH2:10][C:11](O)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].F[P-](F)(F)(F)(F)F.FC1N(C)CC[NH+]1C.CN(C=O)C.O.[NH2:45][NH2:46]>C(N(CC)CC)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])[CH2:10][C:11]([NH:45][NH2:46])=[O:12])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24654Hydrazine hydrate (1:1)HCID 7146288(R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acid2×HCID 44558572HCID 44558572, compound

Product 1

HCID 57973796HCID 57973796, compound

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

A dried flask was charged with 1.00 g (3 mmol) of (3R)-3-[(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid (Intermediate 3) and 865 mg (3.3 mmol) of 2-fluoro-1,3-dimethylimidazolidinium hexafluorophosphate, followed by 7.5 mL of anhydrous DMF. The resulting solution was stirred under nitrogen gas with cooling in an ice bath as 0.835 mL of triethylamine was added by syringe through a septum, and this was followed by 0.291 mL (300 mg, 6 mmol) of hydrazine hydrate. After several min, the ice bath was removed, and the mixture was allowed to warm to room temperature. After 1 h, 40 mL of water was added very gradually by syringe, accompanied by vigorous stirring. This resulted in precipitation of product. One hour later, the solid was collected on a filter, washed generously with water, and dried. The crude product was dissolved in dichloromethane-methanol and evaporated onto several grams of silica gel, which was loaded onto the top of a silica gel column. Flash chromatography (1-4% methanol in dichloromethane) provided the title compound as a white solid, mp 168-168.5° C. LC-MS 248 (M+1-Boc).

Workup

  1. additionwas added by syringe through a septum
  2. customAfter several min, the ice bath was removed
  3. addition40 mL of water was added very gradually by syringe
  4. customThis resulted in precipitation of product
  5. customOne hour later, the solid was collected on a filter
  6. washwashed generously with water
  7. customdried
  8. dissolutionThe crude product was dissolved in dichloromethane-methanol
  9. customevaporated onto several grams of silica gel, which

Sources & evidence

ORD record
ord-d5a1850137e84a0f8ec520406a1fd9fb
Source dataset
uspto-grants-2009_12
Patent number
US07625888B2

Reaction notes

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