Bromotrimethylsilane → HCID 22237383, compound

HRID 1281397Notes

Reaction equation

HRID 1281397 reaction equation
COC[O:4][C:5]1[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=2)=[CH:9][C:8]([C:18](=[O:36])[NH:19][CH2:20][C:21]2([CH2:24][O:25][CH2:26][CH2:27][CH2:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:23][CH2:22]2)=[CH:7][C:6]=1[C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([Cl:43])[CH:38]=1.C[Si](Br)(C)C>C(Cl)Cl>[Cl:17][C:13]1[CH:12]=[C:11]([C:10]2[CH:9]=[C:8]([C:18](=[O:36])[NH:19][CH2:20][C:21]3([CH2:24][O:25][CH2:26][CH2:27][CH2:28][CH2:29][C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)[CH2:22][CH2:23]3)[CH:7]=[C:6]([C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([Cl:43])[CH:38]=3)[C:5]=2[OH:4])[CH:16]=[CH:15][CH:14]=1

Participants

4

Reactant 2

HCID 76113BromotrimethylsilaneHCID 22237418HCID 22237418, compound

Product 1

HCID 22237383HCID 22237383, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (3,3″-dichloro-5′-{[1-(4-phenylbutoxymethyl)-cyclopropylmethyl]-carbamoyl}-[1,1′;3′1″]terphenyl-2′-yloxy)methyl methyl ether (0.681 g, 1.10 mmol) in CH2Cl2 (15 mL) at −30° C. containing 4 Å molecular sieves was added trimethylsilyl bromide (0.581 mL, 4.40 mmol). After stirring at this temperature for 1 h, it was warmed to 0° C. and stirred an additional 5 h. Only slight conversion to product so warmed to room temperature and stirred at this temperature for 18 h. At this point, the mixture was quenched with sat. aq. NaHCO3 (10 mL) and extracted with EtOAc (250 mL). The organic layer was washed with brine (25 mL) and dried (MgSO4). After concentration, the residue was purified by the Biotage Flash 40 apparatus (10 to 30% EtOAc/petroleum ether gradient) to afford the product (0.455 g, 72%) as a solid; 1H NMR (DMSO-d6) δ 0.32-0.41 (m, 2H), 0.47-0.55 (m, 2H), 1.40-1.62 (m, 4H), 2.46-2.58 (m, 2H), 3.28 (s, 2H), 3.28-3.42 (m, 4H), 7.11-7.20 (m, 3H), 7.20-7.29 (m, 2H), 7.42-7.55 (m, 6H), 7.65 (s, 2H), 7.79 (s, 2H), 8.34 (t, J=6.3 Hz, 1H), 9.19 (s, 1H); mass spectrum [(+) ESI], m/z 574 (M)+.

Workup

  1. stirringstirred an additional 5 h
  2. temperatureOnly slight conversion to product so warmed to room temperature
  3. stirringstirred at this temperature for 18 h
  4. customAt this point, the mixture was quenched with sat. aq. NaHCO3 (10 mL)
  5. extractionextracted with EtOAc (250 mL)
  6. washThe organic layer was washed with brine (25 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationAfter concentration
  9. customthe residue was purified by the Biotage Flash 40 apparatus (10 to 30% EtOAc/petroleum ether gradient)

Sources & evidence

ORD record
ord-b12ed138d7864247b90d8aa3a5654aec
Source dataset
uspto-grants-2002_09
Patent number
US06451827B2

Reaction notes

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