Carbon tetrabromide → HCID 117870535, compound

HRID 530647Notes

Reaction equation

HRID 530647 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH:14](O)[C:15]2[CH:16]=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:24]C(Br)(Br)Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH:14]([Br:24])[C:15]2[CH:16]=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 11205Carbon tetrabromideHCID 11776Triphenylphosphine2×HCID 118276758HCID 118276758, compound

Product 1

HCID 117870535HCID 117870535, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(S)-2-[Hydroxy-(6-methoxy-pyridin-3-yl)-methyl]-morpholine-4-carboxylic acid tert-butyl ester (290 mg, 0.90 mmol) was dissolved in dichloromethane (5 mL) and cooled to 0° C. Tetrabromomethane (593 mg, 1.79 mmol) was added. Triphenylphosphine (305 mg, 1.16 mmol) was then added portionwise and the resulting reaction mixture was stirred at 0° C. for 10 min., then at room temperature for 1.25 h. Reaction was not complete so additional triphenylphosphine (45 mg) was added and the reaction was stirred at room temperature for 2.5 h. The reaction mixture was concentrated and purified by flash chromatography (1:2 EtOAc/heptane eluent) to afford (S)-2-[bromo-(6-methoxy-pyridin-3-yl)-methyl]-morpholine-4-carboxylic acid tert-butyl ester (295 mg, 85%) as a colorless liquid. The product was a mixture of diastereomers by NMR: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.42 (s, 3.5H) 1.48 (s, 5.5H) 2.54-3.06 (m, 2H) 3.47 (d, J=2.69 Hz, 0.65H) 3.54-3.64 (m, 0.45H) 3.66-3.88 (m, 3H) 3.93 (s, 3H) 3.97-4.06 (m, 0.45H) 4.23-4.48 (m, 0.55H) 4.83 (d, J=7.25 Hz, 1H) 6.70-6.78 (m, 1H) 7.69 (dd, J=8.60, 2.69 Hz, 1H) 8.13 (d, J=2.42 Hz, 1H).

Workup

  1. customthe resulting reaction mixture
  2. waitat room temperature for 1.25 h
  3. customReaction
  4. additionwas added
  5. stirringthe reaction was stirred at room temperature for 2.5 h
  6. concentrationThe reaction mixture was concentrated
  7. custompurified by flash chromatography (1:2 EtOAc/heptane eluent)

Sources & evidence

ORD record
ord-cf3c6a4057cc4d079cdc4a57dfecba7d
Source dataset
uspto-grants-2016_05
Patent number
US09353096B2

Reaction notes

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