Diisopropylethylamine → (R)-tert-butyl 3-((1S,2S)-2-(3,5-difluorobenzyl)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-3-oxopropyl)-3,4-dihydro-isoquinoline-2(1H)-carboxylate

HRID 601701Notes

Reaction equation

HRID 601701 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:25])[CH2:15][CH2:16][C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([F:24])[CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(OS(C(F)(F)F)(=O)=O)(CCCC)CCCC.CCN(C(C)C)C(C)C.[C:52]([O:56][C:57]([N:59]1[C@@H:68]([C:69](O)=[O:70])[CH2:67][C:66]2[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=2)[CH2:60]1)=[O:58])([CH3:55])([CH3:54])[CH3:53]>C(Cl)Cl.CO>[F:24][C:19]1[CH:18]=[C:17]([CH:22]=[C:21]([F:23])[CH:20]=1)[CH2:16][C@H:15]([C:14]([N:9]1[C@@H:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:12][O:11][C:10]1=[O:13])=[O:25])[C@@H:69]([C@H:68]1[CH2:67][C:66]2[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=2)[CH2:60][N:59]1[C:57]([O:56][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:58])[OH:70]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 688607(3R)-2-[(tert-butoxy)carbonyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acidHCID 2724243Methanesulfonic acid, 1,1,1-trifluoro-, anhydride with B,B-dibutylborinic acidHCID 59733915(S)-4-benzyl-3-(3-(3,5-difluorophenyl)propanoyl)oxazolidin-2-one

Product 1

HCID 67271761(R)-tert-butyl 3-((1S,2S)-2-(3,5-difluorobenzyl)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-3-oxopropyl)-3,4-dihydro-isoquinoline-2(1H)-carboxylateYield 78%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of (S)-4-benzyl-3-(3-(3,5-difluorophenyl)propanoyl)oxazolidin-2-one (preparation D, 1.3 g, 3.77 mmol) in CH2Cl2 (50 mL) at −78° C. was added Bu2BOTf (4.90 ml, 4.90 mmol, 1M in CH2Cl2) and Hunig's base (972 mg, 7.54 mmol). The resulting mixture was brought up to 0° C. and stirred for 20 min. The mixture was cooled back to −78° C. and a solution of (R)-tert-butyl 3-formyl-3,4-dihydroisoquinoline-2(1H)-carboxylate (Step A (3), 1.10 g, 4.20 mmol) in CH2Cl2 (50 mL) was added dropwise. When the addition was complete, the mixture was allowed to warm to rt. After stirring at rt for 1 h, MeOH was added and the mixture was concentrated in vacuo. The crude mixture was purified by silica gel Flash chromatography to give 1.78 g (78% yield) of the title compound. MS (ESI)(M+H)+ 607.20.

Workup

  1. customwas brought up to 0° C.
  2. additionWhen the addition
  3. temperatureto warm to rt
  4. stirringAfter stirring at rt for 1 h
  5. concentrationthe mixture was concentrated in vacuo
  6. customThe crude mixture was purified by silica gel Flash chromatography

Sources & evidence

ORD record
ord-a02cfd3177544ce7b45db2a0baa78c22
Source dataset
uspto-grants-2011_03
Patent number
US07902218B2

Reaction notes

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