Trifluoroacetic acid → (3S)-benzyl 4-(2-hydroxy-2-((R)-3-methyl-1-oxoisochroman-6-yl)ethyl)-3-(hydroxymethyl)piperazine-1-carboxylate

HRID 1501966Notes

Reaction equation

HRID 1501966 reaction equation
[OH:1][CH:2]([C:19]1[CH:20]=[C:21]2[C:26](=[CH:27][CH:28]=1)[C:25](=[O:29])[O:24][C@H:23]([CH3:30])[CH2:22]2)[CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12]C(C)(C)C)=[O:11])[CH2:6][C@H:5]1[CH2:17][OH:18].FC(F)(F)C(O)=O.C(N(CC)CC)C.ClC(O[CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)=O>C(Cl)Cl>[OH:1][CH:2]([C:19]1[CH:20]=[C:21]2[C:26](=[CH:27][CH:28]=1)[C:25](=[O:29])[O:24][C@H:23]([CH3:30])[CH2:22]2)[CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][CH2:49][C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)=[O:11])[CH2:6][C@H:5]1[CH2:17][OH:18]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 86727029tert-butyl (3S)-3-(hydroxymethyl)-4-{2-hydroxy-2-[(3R)-3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl]ethyl}piperazine-1-carboxylate

Product 1

HCID 131734288(3S)-benzyl 4-(2-hydroxy-2-((R)-3-methyl-1-oxoisochroman-6-yl)ethyl)-3-(hydroxymethyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the solution of (3S)-tert-butyl 4-(2-hydroxy-2-((R)-3-methyl-1-oxoisochroman-6-yl)ethyl)-3-(hydroxymethyl)piperazine-1-carboxylate (2630 mg, 6.25 mmol) in methylene chloride (10 mL) was added trifluoroacetic acid (10 mL, 130 mmol) at rt for 1 h. After removing the volatile the residue was dissolved in methylene chloride (100 mL). To the above solution was added triethylamine (4.36 mL, 31.3 mmol) and benzyl chloroformate (0.986 mL, 6.56 mmol) at 0° C. for 0.5 h. The reaction was quenched by water followed by addition of saturated sodium carbonate. The mixture was extracted with methylene chloride, dried over sodium sulfate, concentrated and the residue was purified on Biotage using 40-100% EtOAc/hexane to give the title compound: LC/MS: (M+1)+: 455.10.

Workup

  1. customAfter removing the volatile the residue
  2. dissolutionwas dissolved in methylene chloride (100 mL)
  3. customThe reaction was quenched by water
  4. additionfollowed by addition of saturated sodium carbonate
  5. extractionThe mixture was extracted with methylene chloride
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customthe residue was purified on Biotage

Sources & evidence

ORD record
ord-d1a9a393b8c64716ba80eeb3fc6c24e1
Source dataset
uspto-grants-2015_12
Patent number
US09206199B2

Reaction notes

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