Acetic Acid → 1-Methyl-8-(phenylsulfonyl)-1,3,4,8-tetrahydro-2H-[1,4]oxazepino[6,7-e]indole

HRID 2423173Notes

Reaction equation

HRID 2423173 reaction equation
C(O)(=O)C.[CH3:5][C:6]1[C:12]2=[C:13]3[C:17](=[CH:18][CH:19]=[C:11]2[O:10][CH2:9][CH2:8][N:7]=1)[N:16]([S:20]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)(=[O:22])=[O:21])[CH:15]=[CH:14]3.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:5][CH:6]1[C:12]2=[C:13]3[C:17](=[CH:18][CH:19]=[C:11]2[O:10][CH2:9][CH2:8][NH:7]1)[N:16]([S:20]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)(=[O:22])=[O:21])[CH:15]=[CH:14]3

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 250545001-methyl-8-(phenylsulfonyl)-3,8-dihydro-4H-[1,4]oxazepino[6,7-e]indole

Product 1

HCID 250542401-Methyl-8-(phenylsulfonyl)-1,3,4,8-tetrahydro-2H-[1,4]oxazepino[6,7-e]indoleYield 37.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1,1′-Azobis(N,N-dimethylformamide) (73 mg, 0.43 mmol) was added to a solution of 1-[5-hydroxy-1-(phenylsulfonyl)-1H-indol-4-yl]ethanone (Intermediate 23, 67 mg, 0.21 mmol), tert-butyl N-(2-hydroxy-ethyl)carbamate (0.14 g, 0.85 mmol) and triphenylphosphine (112 mg, 0.430 mmol) in DCM (5 mL). The mixture was heated at 43° C. for 1 hour and additional 1,1′-azobis(N,N-dimethylformamide) (0.030 g, 0.17 mmol) was added and the mixture was heated at 43° C. for an additional 2 hours. The mixture was cooled to room temperature and TFA (2.5 mL) was added and the mixture was stirred for 1 hour and evaporated. The residue was partitioned between DCM and 1 M NaOH. The organic phase was dried (MgSO4) and evaporated. The crude product was purified by flash chromatography using 5% MeOH in DCM as the eluent to give 75 mg of 1-methyl-8-(phenylsulfonyl)-3,8-dihydro-4H-[1,4]oxazepino[6,7-e]indole. Acetic acid (132 mg, 2.20 mmol) was added to a solution of the 1-methyl-8-(phenylsulfonyl)-3,8-dihydro-4H-[1,4]oxazepino[6,7-e]indole (75.0 mg, 0.22 mmol) in DCM (10 mL) and the mixture was allowed to stir for 10 minutes at room temperature before sodium triacetoxyborohydride (0.070 g, 0.33 mmol) was added all in one portion. The mixture was stirred for 30 minutes and transferred to a separation funnel and washed with 1 M NaOH and brine. The organic phase was dried (MgSO4) and evaporated. The crude product was purified by flash chromatography on silica gel using MeOH:DCM:NEt3 (5:94:1) as the eluent to give the title compound (28 mg) as a white solid. MS m/z 343 [M+H]+.

Workup

  1. additionwas added all in one portion
  2. customtransferred to a separation funnel
  3. washwashed with 1 M NaOH and brine
  4. dry with materialThe organic phase was dried (MgSO4)
  5. customevaporated
  6. customThe crude product was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-58ece44dad8444938bf54014f464e0fb
Source dataset
uspto-grants-2011_06
Patent number
US07960374B2

Reaction notes

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