Diisopropylethylamine → 9H-Fluoren-9-ylmethyl[(1S,2R)-2-{[(4-bromo-5-ethylthiophen-2-yl)carbonyl]amino}-3,3-difluorocyclohexyl]carbamate

HRID 2046411Notes

Reaction equation

HRID 2046411 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:9]([OH:11])=O)[S:5][C:6]=1[CH2:7][CH3:8].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[Cl-].[CH:40]1[C:52]2[CH:51]([CH2:53][O:54][C:55]([NH:57][C@@H:58]3[C@@H:63]([NH3+:64])[C:62]([F:66])([F:65])[CH2:61][CH2:60][CH2:59]3)=[O:56])[C:50]3[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=3)[C:44]=2[CH:43]=[CH:42][CH:41]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[CH:40]1[C:52]2[CH:51]([CH2:53][O:54][C:55](=[O:56])[NH:57][C@H:58]3[CH2:59][CH2:60][CH2:61][C:62]([F:66])([F:65])[C@@H:63]3[NH:64][C:9]([C:4]3[S:5][C:6]([CH2:7][CH3:8])=[C:2]([Br:1])[CH:3]=3)=[O:11])[C:50]3[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=3)[C:44]=2[CH:43]=[CH:42][CH:41]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 37663724-Bromo-5-ethylthiophene-2-carboxylic acidHCID 67123027(1R,6S)-6-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-2,2-difluorocyclohexanaminium chloride

Product 1

HCID 671452049H-Fluoren-9-ylmethyl[(1S,2R)-2-{[(4-bromo-5-ethylthiophen-2-yl)carbonyl]amino}-3,3-difluorocyclohexyl]carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-Bromo-5-ethylthiophene-2-carboxylic acid (300 mg, 1.15 mmol) and BOP (762 mg, 1.72 mmol) were dissolved in DMF (11.5 mL) and stirred at room temperature for 5 minutes. (1R,6S)-6-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-2,2-difluorocyclohexanaminium chloride (432 mg, 1.16 mmol) was added followed by diisopropylethyl amine (0.50 mL, 2.87 mmol) and the solution was stirred at room temperature for 18 h. The solution was diluted with water, and extracted with dichloromethane (×3). The organic layers were collected, dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography affording the title compound as an orange oil. 1H NMR (500 MHz, CDCl3) δ 7.72 (d, 2H); 7.46 (dd, 2H); 7.36 (s, 1H); 7.35 (d, 2H); 7.23 (dd, 2H); 6.36 (d, 1H); 5.14 (d, 1H); 4.36 (dd, 1H); 4.29 (dd, 1H); 4.13 (dd, 1H); 4.01 (dd, 1H); 3.86 (dd, 1H); 2.70 (q, 2H); 2.82 (m, 1H); 2.17 (m, 1H); 1.86 (m, 2H); 1.65 (m, 1H); 1.43 (m, 1H); 1.18 (t, 3H). LRMS (APCI) calc'd for (C28H27BrF2N2O3S) [M+H]+, 589.1. found 589.1.

Workup

  1. stirringthe solution was stirred at room temperature for 18 h
  2. extractionextracted with dichloromethane (×3)
  3. customThe organic layers were collected
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-28287c85da9e47c69d636daa769607fb
Source dataset
uspto-grants-2013_11
Patent number
US08592425B2

Reaction notes

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