Methanol → 7-bromo-5-(2-fluorophenyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

HRID 1365059Notes

Reaction equation

HRID 1365059 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][CH2:10][CH2:9][N:8]=[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[F:18])[C:6]=2[CH:19]=1.CO.[BH4-].[Na+]>C(O)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][CH2:10][CH2:9][NH:8][CH:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[F:18])[C:6]=2[CH:19]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydride2×HCID 577324247-bromo-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine

Product 1

HCID 577324237-bromo-5-(2-fluorophenyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepineYield 63.4%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A round bottomed flask was charged with 7-bromo-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine (47 mg), methanol (5 mL) and acetic acid (1 mL). The resulting mixture was treated with sodium borohydride in small portions while stirring at room temperature. The addition of sodium borohydride was continued until the starting material was consumed. The reaction was then concentrated to dryness and taken up in a saturated solution of sodium bicarbonate. The aqueous mixture was stirred for 10 minutes then extracted with ethyl acetate. The combined organic extracts were dried over magnesium sulfate, filtered and concentrated to an oil. Silica gel purification provided 7-bromo-5-(2-fluorophenyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine (30 mg) as a colorless oil. H1 NMR (d6-dmso): 7.47 (t, 1H), 7.34 (q, 1H), 7.10-7.25 (m, 3H), 6.88 (d, 1H), 6.40 (s, 1H), 5.66 (d, 1H), 5.04 (br s, 1H), 3.20 (m, 1H), 2.95 (m, 1H), 2.76 (m, 2H), 2.60 (br s, 1H).

Workup

  1. customwas consumed
  2. concentrationThe reaction was then concentrated to dryness
  3. stirringThe aqueous mixture was stirred for 10 minutes
  4. extractionthen extracted with ethyl acetate
  5. dry with materialThe combined organic extracts were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to an oil
  8. customSilica gel purification

Sources & evidence

ORD record
ord-cc8cadbfed3d4344aab14839e28da0f0
Source dataset
uspto-grants-2011_02
Patent number
US07888503B2

Reaction notes

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