Trimethylphosphine → HCID 69281638, compound

HRID 2362404Notes

Reaction equation

HRID 2362404 reaction equation
[N:1]([C@H:4]([C:16]1[CH:17]=[N:18][CH:19]=[C:20]([Br:22])[CH:21]=1)[C@:5]([C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[F:15])([OH:7])[CH3:6])=[N+]=[N-].CP(C)C>O1CCCC1.CCOCC>[NH2:1][C@H:4]([C:16]1[CH:17]=[N:18][CH:19]=[C:20]([Br:22])[CH:21]=1)[C@:5]([C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[F:15])([OH:7])[CH3:6]

Participants

5

Reactant 2

HCID 68983TrimethylphosphineHCID 86673435HCID 86673435, compound

Product 1

HCID 69281638HCID 69281638, compoundYield 93.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1R,2S)-1-azido-1-(5-bromopyridin-3-yl)-2-(2,5-difluorophenyl)propan-2-ol (44 mg, 0.119 mmol) in tetrahydrofuran (2 mL) at 0° C. was added trimethylphosphine (0.179 mL, 0.179 mmol) drop wise. Ice bath was removed once no more nitrogen gas come out. One hour later, water (0.1000 mL) was added and continuously stirred for 18 hours. The reaction mixture was concentrated to afford a yellow oil that was redissolved in 5 mL ether then washed with 10 mL water. The ether layer was dried by magnesium sulfate, filtered, and concentrated to provide a light yellow of (1R,2S)-1-amino-1-(5-bromopyridin-3-yl)-2-(2,5-difluorophenyl)propan-2-ol (42.2 mg, 0.111 mmol, 93% yield). 1H NMR (500 MHz, DMSO-d6) δ 8.36 (d, J=2.1 Hz, 1H), 8.01 (d, J=1.8 Hz, 1H), 7.73 (t, J=2.0 Hz, 1H), 7.15 (ddd, J=11.1, 8.9, 4.7 Hz, 1H), 7.06-6.98 (m, 1H), 6.90 (ddd, J=9.9, 6.3, 3.4 Hz, 1H), 5.70 (s, 1H), 4.13 (s, 1H), 3.33 (s, 2H), 1.65 (d, J=1.5 Hz, 3H), Mass spec.: 345.1 (MH)+.

Workup

  1. customIce bath was removed once no more nitrogen gas
  2. additionOne hour later, water (0.1000 mL) was added
  3. concentrationThe reaction mixture was concentrated
  4. customto afford a yellow oil that
  5. washthen washed with 10 mL water
  6. dry with materialThe ether layer was dried by magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-7c59a56d53d74b9f9b01a6c3cbb645b6
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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