N,N,N',N'-Tetramethylazodicarboxamide → (3S)-3-Methyl-8-(phenylsulfonyl)-1,3,4,8-tetrahydro-2H-[1,4]oxazepino [6,7-e]indole

HRID 2423128Notes

Reaction equation

HRID 2423128 reaction equation
[N:1](C(N(C)C)=O)=NC(N(C)C)=O.[OH:13][C:14]1[CH:22]=[CH:21][C:20]2[N:19]([S:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)(=[O:25])=[O:24])[CH:18]=[CH:17][C:16]=2[C:15]=1[CH:32]=O.[C:34]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:39]=CC=C[CH:35]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:35][C@@H:34]1[NH:1][CH2:32][C:15]2=[C:16]3[C:20](=[CH:21][CH:22]=[C:14]2[O:13][CH2:39]1)[N:19]([S:23]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)(=[O:25])=[O:24])[CH:18]=[CH:17]3

Participants

6

Reactant 4

HCID 4278N,N,N',N'-TetramethylazodicarboxamideHCID 11776TriphenylphosphineHCID 5049666Sodium triacetoxyborohydrideHCID 866217145-Hydroxy-1-(phenylsulfonyl)-1H-indole-4-carbaldehyde2×

Product 1

HCID 25057081(3S)-3-Methyl-8-(phenylsulfonyl)-1,3,4,8-tetrahydro-2H-[1,4]oxazepino [6,7-e]indoleYield 27.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
45 °C

Procedure

1,1′-Azobis(N,N-dimethylformamide) (57 mg, 0.33 mmol) was added to a solution of 5-hydroxy-1-(phenylsulfonyl)-1H-indole-4-carbaldehyde (Intermediate 10, 0.050 g, 0.16 mmol), S-(−)-2-(tert-butoxycarbonylamino)-1-propanol (58 mg, 0.33 mmol) and triphenylphosphine (87 mg, 0.33 mmol) in DCM (5 mL). The mixture was stirred at 45° C. for 2 days and the mixture was evaporated. The crude material was purified by flash chromatography using 1% to 2.5% MeOH in DCM. This boc-protected intermediate was dissolved in DCM (3 mL) and TFA (1 mL) was added. The mixture was stirred for 1 hour and evaporated. The residue was dissolved in THF (3 mL) and sodium triacetoxyborohydride (30.0 mg, 0.141 mmol) was added all in one portion. The reaction mixture was stirred for 20 minutes 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 a light yellow solid (15 mg) of the title compound. MS m/z 343 [M+H]+.

Workup

  1. customthe mixture was evaporated
  2. customThe crude material was purified by flash chromatography
  3. dissolutionwas dissolved in DCM (3 mL)
  4. additionTFA (1 mL) was added
  5. stirringThe mixture was stirred for 1 hour
  6. customevaporated
  7. dissolutionThe residue was dissolved in THF (3 mL)
  8. stirringThe reaction mixture was stirred for 20 minutes
  9. customevaporated
  10. customThe crude product was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-da8b7c232c3740adb3ba719726210130
Source dataset
uspto-grants-2011_06
Patent number
US07960374B2

Reaction notes

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