Boron tribromide → HCID 69706140, compound

HRID 723160Notes

Reaction equation

HRID 723160 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[C:8]([C:11]1[S:15][C:14]([S:16][CH3:17])=[C:13]([S:18]([C:21]2[CH:22]=[C:23]([C:27]3[C:32]([CH3:33])=[CH:31][C:30]([O:34]C)=[CH:29][C:28]=3[CH2:36][O:37][CH2:38][C:39]([OH:41])=[O:40])[CH:24]=[CH:25][CH:26]=2)(=[O:20])=[O:19])[CH:12]=1)(=[NH:10])[NH2:9].B(Br)(Br)Br>C(Cl)Cl>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[C:8]([C:11]1[S:15][C:14]([S:16][CH3:17])=[C:13]([S:18]([C:21]2[CH:22]=[C:23]([C:27]3[C:32]([CH3:33])=[CH:31][C:30]([OH:34])=[CH:29][C:28]=3[CH2:36][O:37][CH2:38][C:39]([OH:41])=[O:40])[CH:24]=[CH:25][CH:26]=2)(=[O:19])=[O:20])[CH:12]=1)(=[NH:9])[NH2:10]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 69586648HCID 69586648, compound

Product 1

HCID 69706140HCID 69706140, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of [3′-(5-carbamimidoyl-2-methylsulfanyl-thiophene-3-sulfonyl)-4-methoxy-6-methyl-biphenyl-2-ylmethoxy]-acetic acid ((Example 192: step g) 0.077 g, 0.0148 mmol) in dry CH2Cl2 (10 mL) was cooled to 0° C. and treated with BBr3 (0.592 mL, 0.592 mmol) dropwise. The reaction stirred at 0° C. for 30 min. then was allowed to warm to room temperature and stir 27 h. The reaction mixture was cooled to 0° C. and quenched with MeOH. Some HBr evolution was seen. All solvents were evaporated in vacuo, and the residue was taken up in EtOAc (100 mL) and washed with water (1×75 mL) and brine (2×50 mL). The organic layer was dried over MgSO4 and concentrated in vacuo. Preparatory HPLC (5–50% acetonitrile in 1% TFA/water over 30 min.) afforded the product [3′-(5-carbamimidoyl-2-methylsulfanyl-thiophene-3-sulfonyl)-4-hydroxy-6-methyl-biphenyl-2-ylmethoxy]-acetic acid trifloroacetate (0.039, 52%) as a white glassy solid. 1H NMR (MeOD): δ 8.344 (s, 1H), 8.090 (d, 1H, J=8.0 Hz), 7.877 (t, 1H, J=2.0 Hz), 7.721 (t, 1H, J=7.6 Hz), 7.572 (d, 1H, J=7.6 Hz), 6.778 (d, 1H, J=2.8 Hz), 6.735 (d, 1H, J=2.0 Hz), 2.710 (s, 3H), 2.028 (s, 2H), 1.935 (s, 3H), 1.254 (t, 2H, J=7.6 Hz).

Workup

  1. temperatureto warm to room temperature
  2. stirringstir 27 h
  3. temperatureThe reaction mixture was cooled to 0° C.
  4. customquenched with MeOH
  5. customAll solvents were evaporated in vacuo
  6. washwashed with water (1×75 mL) and brine (2×50 mL)
  7. dry with materialThe organic layer was dried over MgSO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c8cf8b7258ed429aa2c51d917058e391
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

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