Benzyl Bromide → HCID 131734550, compound

HRID 592117Notes

Reaction equation

HRID 592117 reaction equation
[C:1]([O:9][C@@H:10]1[C@@H:27]([O:28][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[C@H:26]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C@@H:25]([CH2:44][OH:45])[O:24][C@H:11]1[S:12][C:13]1[CH:18]=[C:17]([C:19]([CH3:22])([CH3:21])[CH3:20])[CH:16]=[CH:15][C:14]=1[CH3:23])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:46]1[CH:51]=[CH:50][C:49]([CH2:52]Br)=[CH:48][CH:47]=1.[H-].[Na+]>C1COCC1.CN(C=O)C>[C:1]([O:9][C@@H:10]1[C@@H:27]([O:28][Si:29]([C:32]([CH3:33])([CH3:34])[CH3:35])([CH3:30])[CH3:31])[C@H:26]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C@@H:25]([CH2:44][O:45][CH2:52][C:49]2[CH:50]=[CH:51][CH:46]=[CH:47][CH:48]=2)[O:24][C@H:11]1[S:12][C:13]1[CH:18]=[C:17]([C:19]([CH3:20])([CH3:21])[CH3:22])[CH:16]=[CH:15][C:14]=1[CH3:23])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 7498Benzyl Bromide2×HCID 24758Sodium hydrideHCID 131734551HCID 131734551, compound

Product 1

HCID 131734550HCID 131734550, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

To a solution of crude 28 (approx. 1.23 mmol) in THF/DMF (9:1, 10 ml) at 0° C., BnBr (0.18 ml, 1.50 mmol) and NaH (36 mg, 1.50 mmol) were added. The solution was warmed to room temperature over 2 h, then cooled to 0° C. again and further BnBr (0.18 ml, 1.50 mmol) was added. The reaction was warmed to room temperature over 30 min, cooled to 0° C. and quenched by the addition of water. After dilution with Et2O the phases were separated and the aqueous layer extracted with Et2O. The organic phase was then dried over MgSO4, filtered and concentrated. Column chromatography on silica gel (hexanes/ethyl acetate) afforded 29 (797 mg, 1.08 mmol, 88%). 1H-NMR (400 MHz, CDCl3) δ 8.14-7.00 (m, 18H, Ar—H), 5.31 (dd, 1H, J1=10.1 Hz, J2=8.9 Hz, 2-H), 4.83 (app. d, 1H, J=11.3 Hz, benzyl-Ha), 4.72 (d, 1H, J=10.2 Hz, 1-H), 4.63 (app. d, 1H, J=11.0 Hz, benzyl-Hb), 4.58 (app. d, 2H, J=3.1 Hz, benzyl-H), 3.95 (app. t, 1H, J=8.7 Hz, 3-H), 3.78-3.51 (m, 4H, 4-H, 5-H, 6-H), 2.15 (s, 3H, S—CH3), 1.25 (s, 9H, S-tBu), 0.79 (s, 9H, TBS-tBu), 0.00 (s, 3H, TBS-CH3), −0.16 (s, 3H, TBS-CH3); 13C-NMR (100 MHz, CDCl3) δ 165.6, 149.7, 138.2, 136.5, 133.2, 130.5, 130.1, 129.8, 129.2, 128.5, 128.4, 128.0, 127.72, 127.68, 127.6, 124.7, 88.0 (C-1), 79.5 (C-5), 78.9 (C-4), 77.0 (C-3), 75.1, 73.6 (C-2), 73.5, 69.0 (C-6), 31.4, 25.8, 20.3, −3.9, −4.1; HRMS (ESI): Calcd for C44H56O6SSiNa+ [M+Na]+ 763.3459. found: 763.3500

Workup

  1. temperaturecooled to 0° C. again
  2. temperatureThe reaction was warmed to room temperature over 30 min
  3. temperaturecooled to 0° C.
  4. customquenched by the addition of water
  5. customAfter dilution with Et2O the phases were separated
  6. extractionthe aqueous layer extracted with Et2O
  7. dry with materialThe organic phase was then dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-303089ef7c3446d088c954a05146e608
Source dataset
uspto-grants-2016_01
Patent number
US09238669B2

Reaction notes

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