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

HRID 1640062Notes

Reaction equation

HRID 1640062 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]([O:19][CH3:20])=[O:18])[CH:15]=3)[CH:10]=[CH:9]2)[CH2:4][CH2:3]1.[CH3:21][O:22][C:23]1[C:32]([CH2:33][CH:34]=O)=[C:31]2[C:26]([C:27](=[O:38])[CH2:28][C:29]([CH3:37])([CH3:36])[O:30]2)=[CH:25][CH:24]=1.O1CCCC1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O.C1(C)C=CC=CC=1.C(O)(=O)C>[CH3:21][O:22][C:23]1[C:32]([CH2:33][CH2:34][N:2]2[CH2:3][CH2:4][CH:5]([N:8]3[C:16]4[C:11](=[CH:12][CH:13]=[C:14]([C:17]([O:19][CH3:20])=[O:18])[CH:15]=4)[CH:10]=[CH:9]3)[CH2:6][CH2:7]2)=[C:31]2[C:26]([C:27](=[O:38])[CH2:28][C:29]([CH3:37])([CH3:36])[O:30]2)=[CH:25][CH:24]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 5049666Sodium triacetoxyborohydrideHCID 57682772(7-Methoxy-2,2-dimethyl-4-oxochroman-8-yl)acetaldehydeHCID 66720891methyl 1-piperidin-4-yl-1H-indole-6-carboxylate hydrochloride

Product 1

HCID 59439452methyl 1-{1-[2-(7-methoxy-2,2-dimethyl-4-oxochroman-8-yl)ethyl]piperidin-4-yl}-1H-indole-6-carboxylateYield 98.8%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
40 °C

Procedure

2.92 g of methyl 1-piperidin-4-yl-1H-indole-6-carboxylate hydrochloride and 2.92 g of (7-methoxy-2,2-dimethyl-4-oxochroman-8-yl)acetaldehyde were added with 58.4 mL of tetrahydrofuran and 14.6 mL of acetic acid warmed to 40° C. and the reaction mixture was stirred for about 3 hours. The reaction mixture was cooled with an ice-water bath, and 2.52 g of sodium triacetoxyborohydride was added portionwise divided into three. The reaction mixture was warmed to room temperature and 30 minutes later, progress of the reaction was confirmed. The reaction mixture was cooled with an ice-water bath again and 87 mL of toluene and 29 mL of water were added thereto and the aqueous layer was discarded. The organic layer was washed with 49 mL, 69 mL, 30 mL of 1 N aqueous sodium hydroxide sequentially and then with 29 mL, 14 mL of 5% sodium chloride solution and 14 mL of water. The solvent was evaporated and 4.80 g of the crude title compound was obtained.

Workup

  1. temperatureThe reaction mixture was cooled with an ice-water bath
  2. temperatureThe reaction mixture was warmed to room temperature and 30 minutes later
  3. temperatureThe reaction mixture was cooled with an ice-water bath again
  4. washThe organic layer was washed with 49 mL, 69 mL, 30 mL of 1 N aqueous sodium hydroxide sequentially
  5. customThe solvent was evaporated

Sources & evidence

ORD record
ord-5633f7b5a04e47b28610fabd2a9c1869
Source dataset
uspto-grants-2012_02
Patent number
US08110688B2

Reaction notes

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