Tetrahydrofuran → methyl 1-{1-[2-(7-methoxy-2,2-dimethyl-4-oxochroman-8-yl)ethyl]piperidin-4-yl}-1H-indole-6-carboxylate

HRID 1640064Notes

Reaction equation

HRID 1640064 reaction equation
COCCOC.O1CCCC1.[NH:12]1[CH2:17][CH2:16][CH:15]([N:18]2[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([C:27]([O:29][CH3:30])=[O:28])[CH:25]=3)[CH:20]=[CH:19]2)[CH2:14][CH2:13]1.[CH3:31][O:32][C:33]1[C:42]([CH2:43][CH:44]=O)=[C:41]2[C:36]([C:37](=[O:48])[CH2:38][C:39]([CH3:47])([CH3:46])[O:40]2)=[CH:35][CH:34]=1>C(O)(=O)C>[CH3:31][O:32][C:33]1[C:42]([CH2:43][CH2:44][N:12]2[CH2:13][CH2:14][CH:15]([N:18]3[C:26]4[C:21](=[CH:22][CH:23]=[C:24]([C:27]([O:29][CH3:30])=[O:28])[CH:25]=4)[CH:20]=[CH:19]3)[CH2:16][CH2:17]2)=[C:41]2[C:36]([C:37](=[O:48])[CH2:38][C:39]([CH3:47])([CH3:46])[O:40]2)=[CH:35][CH:34]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 80711,2-DimethoxyethaneHCID 57682772(7-Methoxy-2,2-dimethyl-4-oxochroman-8-yl)acetaldehydeHCID 59439474methyl 1-piperidin-4-yl-1H-indole-6-carboxylate

Product 1

HCID 59439452methyl 1-{1-[2-(7-methoxy-2,2-dimethyl-4-oxochroman-8-yl)ethyl]piperidin-4-yl}-1H-indole-6-carboxylateYield 105.7%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

28 mL of DME, 14 mL of tetrahydrofuran and 1.24 mL of acetic acid were added to 2.80 g of methyl 1-piperidin-4-yl-1H-indole-6-carboxylate and 3.16 g of (7-methoxy-2,2-dimethyl-4-oxochroman-8-yl)acetaldehyde. Although crystals precipitated, the reaction mixture was stirred for one hour as it was. The reaction mixture was cooled with an ice-water bath, and 2.75 g of sodium triacetoxyborohydride was added portionwise divided into three to the reaction mixture. The reaction mixture was warmed to room temperature and added with 3 mL of tetrahydrofuran and about 1.5 hours later, progress of the reaction was confirmed. The reaction mixture cooled with an ice-water bath again and added with 68 mL of toluene and 29 mL of water and, after clarification and filtration, added with 30 mL of toluene and the aqueous layer was discarded. The organic layer was washed with 29 mL of 1 N aqueous sodium hydroxide, 29 mL×2 of 5% sodium chloride solution and 29 mL of water. The solvent was evaporated and 5.62 g of the crude title compound was obtained.

Workup

  1. customAlthough crystals precipitated
  2. temperatureThe reaction mixture was cooled with an ice-water bath
  3. addition2.75 g of sodium triacetoxyborohydride was added portionwise
  4. additionadded with 3 mL of tetrahydrofuran and about 1.5 hours later
  5. temperatureThe reaction mixture cooled with an ice-water bath again
  6. additionadded with 68 mL of toluene and 29 mL of water
  7. filtrationafter clarification and filtration
  8. additionadded with 30 mL of toluene
  9. washThe organic layer was washed with 29 mL of 1 N aqueous sodium hydroxide, 29 mL×2 of 5% sodium chloride solution and 29 mL of water
  10. customThe solvent was evaporated

Sources & evidence

ORD record
ord-98bea6103fc042e8b5e96236214a9968
Source dataset
uspto-grants-2012_02
Patent number
US08110688B2

Reaction notes

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