Carbonate Ion → (S)-1,1,1-Trifluoro-3-(7-nitro-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-propan-2-ol

HRID 1687134Notes

Reaction equation

HRID 1687134 reaction equation
[N+]([O-])(O)=O.[N+:5]([C:8]1[CH:18]=[CH:17][C:11]2[CH2:12][CH2:13][NH:14][CH2:15][CH2:16][C:10]=2[CH:9]=1)([O-:7])=[O:6].C(=O)([O-])[O-].[F:23][C:24]([F:29])([F:28])[C@@H:25]1[CH2:27][O:26]1>C1COCC1>[F:23][C:24]([F:29])([F:28])[C@@H:25]([OH:26])[CH2:27][N:14]1[CH2:15][CH2:16][C:10]2[CH:9]=[C:8]([N+:5]([O-:7])=[O:6])[CH:18]=[CH:17][C:11]=2[CH2:12][CH2:13]1

Participants

5

Reactant 3

HCID 19660Carbonate IonHCID 7171781(2S)-2-(Trifluoromethyl)oxiraneHCID 855770687-Nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine nitrate

Product 1

HCID 67263600(S)-1,1,1-Trifluoro-3-(7-nitro-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-propan-2-olYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

7-Nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine nitric acid salt (2.01 g, 7.88 mmol, 1.0 eq), was placed in THF (100 mL) and MP-carbonate (7.1 g) was added. The reaction was stirred in a sealable vessel for 1 hour and then (S)-2-trifluoromethyl-oxirane (1.30 g, 11.59 mmol, 1.00 mL, 1.47 eq) was added. The reaction vessel was sealed, stirred at room temperature for 1 hour, and then heated at 50° C. overnight. The reaction was then cooled to room temperature and filtered. The resin was washed with CH2Cl2 (150 mL) and the filtrate was concentrated under reduced pressure. Purification by silica gel chromatography using a gradient of 0-50% EtOAc/hex as the eluting solvent to obtain (S)-1,1,1-trifluoro-3-(7-nitro-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-propan-2-ol as an orange solid (2.27 g, 95%). m.p.=82-85° C.; LCMS (m/e) 305 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 8.06-7.99 (m, 2H), 7.31-7.26 (m, 1H), 4.16-4.02 (m, 2H), 3.15-2.97 (m, 4H), 2.96-2.81 (m, 3H), 2.81-2.67 (m, 3H).

Workup

  1. customThe reaction vessel was sealed
  2. stirringstirred at room temperature for 1 hour
  3. temperatureThe reaction was then cooled to room temperature
  4. filtrationfiltered
  5. washThe resin was washed with CH2Cl2 (150 mL)
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-fea7f433aa2f4363bd573f713ef87e10
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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