Dichloromethane → HCID 68293012, compound

HRID 529467Notes

Reaction equation

HRID 529467 reaction equation
[CH3:1][C:2]([S:32][C:33]([C:46]1C=CC=C[CH:47]=1)(C1C=CC=CC=1)C1C=CC=CC=1)([CH3:31])[C@H:3]([NH:13][C:14](=[O:30])[O:15][CH2:16][CH:17]1[C:29]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:4](=[O:12])[NH:5][CH2:6][CH2:7]CCC=O.C(Cl)Cl.C(O)(C(F)(F)F)=O>CCOC(C)=O>[CH3:1][C:2]1([CH3:31])[S:32][C@H:33]2[CH2:46][CH2:47][CH2:7][CH2:6][N:5]2[C:4](=[O:12])[C@H:3]1[NH:13][C:14](=[O:30])[O:15][CH2:16][CH:17]1[C:29]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[CH:21][CH:22]=2

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 86706199HCID 86706199, compound

Product 1

HCID 68293012HCID 68293012, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a round bottom flask was added (R)-(9H-fluoren-9-yl)methyl 3-methyl-1-oxo-1-(5-oxopentylamino)-3-(tritylthio)butan-2-ylcarbamate (35 mg, 0.050 mmol), DCM (1 mL) and TFA (0.077 mL, 1.0 mmol). The reaction mixture was stirred at rt for 15 min. The reaction mixture was diluted with EtOAc (20 mL) and washed with saturated aqueous NaHCO3 (10 mL), water (10 mL) and saturated aqueous NaCl (10 mL). The organic layer was separated, dried over MgSO4, filtered and concentrated. The residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100% EtOAc/Hex to give (9H-fluoren-9-yl)methyl (3R,9aS)-2,2-dimethyl-4-oxooctahydropyrido[2,1-b][1,3]thiazin-3-ylcarbamate (12 mg, 0.027 mmol, 55% yield) as a white solid. Anal. Calcd. for C25H28N2O3S m/z 436.3. found: 437.2 (M+H)+; 1H NMR (500 MHz, CDCl3) δ ppm 7.78 (d, J=7.15 Hz, 2H), 7.63 (t, J=6.60 Hz, 2H), 7.41 (td, J=7.42, 3.30 Hz, 2H), 7.33 (t, J=7.42 Hz, 2H), 5.84 (d, J=8.80 Hz, 1H), 4.90 (dd, J=8.80, 3.85 Hz, 1H), 4.63 (d, J=8.80 Hz, 1H), 4.54-4.35 (m, 2H), 4.26 (t, J=7.15 Hz, 1H), 4.16-3.99 (m, 1H), 3.22 (ddd, J=13.06, 8.39, 4.40 Hz, 1H), 2.00 (dt, J=8.80, 4.40 Hz, 1H), 1.93-1.81 (m, 1H), 1.80-1.67 (m, 3H), 1.62-1.52 (m, 1H), 1.39-1.24 (m, 3H), 1.19 (s, 3H).

Workup

  1. washwashed with saturated aqueous NaHCO3 (10 mL), water (10 mL) and saturated aqueous NaCl (10 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified
  7. washeluting with a gradient of 0-100% EtOAc/Hex

Sources & evidence

ORD record
ord-599eb8c03c444ef289d2815700ff90d6
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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