Carbon tetrabromide → HCID 58897958, compound

HRID 1874171Notes

Reaction equation

HRID 1874171 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@:15]([NH:30][C:31]([NH:33][C:34]2([CH2:37]O)[CH2:36][CH2:35]2)=[O:32])([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:5]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:7]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(Br)(Br)(Br)[Br:59]>CCOCC>[Br:59][CH2:37][C:34]1([NH:33][C:31]([NH:30][C@@:15]([C:4]2[CH:5]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:7]=[C:2]([F:1])[CH:3]=2)([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:32])[CH2:36][CH2:35]1

Participants

5

Reactant 3

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 23582534HCID 23582534, compound

Product 1

HCID 58897958HCID 58897958, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of (R)-1-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-(1-(hydroxymethyl)cyclopropyl)urea (Example 241, 43 mg, 0.08 mmol) in ether (0.4 mL) was added PPh3 (48 mg, 0.18 mmol) and CBr4 (58 mg, 0.18 mmol) at room temperature. The reaction mixture was stirred for 14 h and concentrated under reduced pressure and purified by ISCO chromatography (4 g column, eluting with 0-15% hexane/EtOAc over 14 min) to yield (R)-1-(1-(bromomethyl)cyclopropyl)-3-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)urea as a white solid (8 mg, 17% yield). LCMS: RT=4.06 min [M+H] 601.2 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm); 1H NMR (400 MHz, CDCl3) ppm 0.82-1.03 (m, 4H), 3.47 (qt, J=12 Hz, 2H), 3.81 (ABqt, J=12 Hz, 2H), 5.01 (s, 1H), 5.39 (s, 1H), 5.86 (t, J=53 Hz, 1H), 6.61-6.78 (m, 2H), 6.80-7.25 (m, 10H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. custompurified by ISCO chromatography (4 g column, eluting with 0-15% hexane/EtOAc over 14 min)

Sources & evidence

ORD record
ord-89617020655b46979116ad393a37934e
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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