Trifluoroacetic acid → (3S)-benzyl 4-(2-(3-cyano-4-fluoro-2-methylphenyl)-2-hydroxyethyl)-3-(hydroxymethyl)piperazine-1-carboxylate

HRID 1502003Notes

Reaction equation

HRID 1502003 reaction equation
[C:1]([C:3]1[C:4]([CH3:28])=[C:5]([CH:10]([OH:27])[CH2:11][N:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20]C(C)(C)C)=[O:19])[CH2:14][C@H:13]2[CH2:25][OH:26])[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].FC(F)(F)C(O)=O.C(N(CC)CC)C.ClC(O[CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=O>C(Cl)Cl>[C:1]([C:3]1[C:4]([CH3:28])=[C:5]([CH:10]([OH:27])[CH2:11][N:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[O:19])[CH2:14][C@H:13]2[CH2:25][OH:26])[CH:6]=[CH:7][C:8]=1[F:9])#[N:2]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 71272768(3S)-tert-butyl 4-(2-(3-cyano-4-fluoro-2-methylphenyl)-2-hydroxyethyl)-3-(hydroxymethyl)piperazine-1-carboxylate

Product 1

HCID 86727052(3S)-benzyl 4-(2-(3-cyano-4-fluoro-2-methylphenyl)-2-hydroxyethyl)-3-(hydroxymethyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3S)-tert-butyl 4-(2-(3-cyano-4-fluoro-2-methylphenyl)-2-hydroxyethyl)-3-(hydroxymethyl)piperazine-1-carboxylate (2.87 g, 7.32 mmol) in methylene chloride (20 mL) was added trifluoroacetic acid (20 mL) at rt, and the resulting solution was stirred at rt for 1 h. After removing the volatile solvents, the residue was dissolved in methylene chloride (50 mL). To the above solution was added triethylamine (6.12 mL, 43.9 mmol) and benzyl chloroformate (1.1 mL, 7.3 mmol) dropwise at 0° C. The reaction solution was stirred at 0° C. for 1 h before quenching with saturated sodium bicarbonate solution (200 mL). The mixture was then extracted with methylene chloride (3×100 mL). The combined organic phase was dried over sodium sulphate and concentrated to give the title compound. LC/MS: (M+1)+:428.18.

Workup

  1. customAfter removing the volatile solvents
  2. dissolutionthe residue was dissolved in methylene chloride (50 mL)
  3. stirringThe reaction solution was stirred at 0° C. for 1 h
  4. custombefore quenching with saturated sodium bicarbonate solution (200 mL)
  5. extractionThe mixture was then extracted with methylene chloride (3×100 mL)
  6. dry with materialThe combined organic phase was dried over sodium sulphate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-c973f326fdd44729bebc0b03e622811f
Source dataset
uspto-grants-2015_12
Patent number
US09206199B2

Reaction notes

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