Benzyl Bromide → HCID 86722361, compound

HRID 718774Notes

Reaction equation

HRID 718774 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:18]3[CH:17]=[C:16]4[CH2:19][CH2:20][CH2:21][C@@H:22]5[CH2:27][C@@:26]([OH:32])([C:28]([F:31])([F:30])[F:29])[CH2:25][CH2:24][C@@:23]5([C:33]#[N:34])[C:15]4=[CH:14][C:13]=3[CH:12]=[N:11]2)=[CH:6][CH:5]=1.Br[CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>CN(C=O)C>[CH2:36]([O:32][C@@:26]1([C:28]([F:31])([F:30])[F:29])[CH2:27][C@H:22]2[CH2:21][CH2:20][CH2:19][C:16]3[C:15](=[CH:14][C:13]4[CH:12]=[N:11][N:10]([C:7]5[CH:6]=[CH:5][C:4]([F:3])=[CH:9][CH:8]=5)[C:18]=4[CH:17]=3)[C@:23]2([C:33]#[N:34])[CH2:24][CH2:25]1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 86722362HCID 86722362, compound

Product 1

HCID 86722361HCID 86722361, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of sodium hydride (60 wt % in oil, 103 mg, 2.57 mmol) in DMF (5 mL) was added a solution of (3R,4aR,12bS)-9-(4-fluorophenyl)-3-hydroxy-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carbonitrile (32, R1=4-Fluorophenyl, R3=Trifluoromethyl) (760 mg, 1.71 mmol) in DMF (15 mL) at a dropwise rate. The reaction was stirred for about 10 min at rt, then (bromomethyl)benzene (0.26 mL, 2.14 mmol) was added. The mixture was stirred for about 1 h. Solvents were removed under reduced pressure. The residue was dissolved in DCM (50 mL) and washed with water (25 mL). The organic layer was dried over Na2SO4, filtered and concentrated onto silica gel (10 g). The crude product was purified on silica gel (40 g) using a gradient of 20-40% EtOAc in heptane. Product fractions were combined and concentrated under reduced pressure to yield (3R,4aR,12bS)-3-(benzyloxy)-9-(4-fluorophenyl)-3-(trifluoromethyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazole-12b-carbonitrile (33, R1=4-Fluorophenyl, R3=Trifluoromethyl, Rx=Benzyl) (890 mg, 97%) as a white solid; LC/MS, method 3, Rt=3.08 min, MS m/z 534 (M+H)+, 1H NMR (400 MHz, DMSO) δ 8.35 (d, J=0.8 Hz, 1H), 8.12 (s, 1H), 7.86-7.78 (m, 2H), 7.71 (s, 1H), 7.48-7.29 (m, 7H), 4.80-4.66 (m, 2H), 3.41-3.31 (m, 1H), 3.13-3.01 (m, 1H), 2.74-2.62 (m, 1H), 2.61-2.51 (m, 1H), 2.29-2.22 (m, 1H), 2.18-1.93 (m, 4H), 1.89-1.70 (m, 3H), 1.42-1.27 (m, 1H).

Workup

  1. stirringThe mixture was stirred for about 1 h
  2. customSolvents were removed under reduced pressure
  3. dissolutionThe residue was dissolved in DCM (50 mL)
  4. washwashed with water (25 mL)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated onto silica gel (10 g)
  8. customThe crude product was purified on silica gel (40 g)
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-aa3f8f72f3344b7987bfc5647fb7854c
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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