Carbon tetrabromide → HCID 59201375, compound

HRID 451711Notes

Reaction equation

HRID 451711 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:8](O)[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1.C(Br)(Br)(Br)[Br:24].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Br:24][CH:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=1)[C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]1

Participants

5

Reactant 3

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 58011554HCID 58011554, compound

Product 1

HCID 59201375HCID 59201375, compoundYield 42.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 250 mL round bottom flask was charged with 0.4845 g (1.56 mmol, 1.0 equiv) of (R)-tert-butyl 3-((R)-(3-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate, 0.7920 g (2.39 mmol, 1.52 equiv) of carbon tetrabromide, and 15 mL of CH2Cl2. The flask was cooled with an ice bath and then 0.6258 g (2.38 mmol, 1.52 equiv) of triphenylphosphine was added in portions over 5 min. The reaction mixture was allowed to slowly warm to rt while stirring overnight. Analysis of the mixture by LC-MS showed two peaks with the same mass 236 [M-C4H8—Br]+, consistent with a ca 62:38 mixture of two isomers: tR=10.48 min and 10.93 min in 16 min chromatography, respectively. After the solvent was removed in vacuo, the residue was purified by ISCO (40 g silica gel column, 0%→30% ethyl acetate/hexanes over 40 min, flow rate 40 mL/min) to afford 0.2470 g (42%) of (3R)-tert-butyl 3-(bromo(3-fluorophenyl)methyl)piperidine-1-carboxylate. MS ESI +ve m/z 236 (M-C4H8—Br). Isomer 1 and 2, MS ESI +ve m/z 236 (M-C4H8—Br), tR=2.13, 2.17 min in 3 min chromatography.

Workup

  1. temperatureThe flask was cooled with an ice bath
  2. additionconsistent with a ca 62:38 mixture of two isomers
  3. waittR=10.48 min and 10.93 min in 16 min chromatography
  4. customAfter the solvent was removed in vacuo
  5. customthe residue was purified by ISCO (40 g silica gel column, 0%→30% ethyl acetate/hexanes over 40 min, flow rate 40 mL/min)

Sources & evidence

ORD record
ord-1fb1cfa2bdd54868bb9f5b657b1a9713
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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