Acetaldehyde → 4-Chloro-2-[ethyl-(2-pyrrolidin-1-yl-ethyl)-amino]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

HRID 1927475Notes

Reaction equation

HRID 1927475 reaction equation
[CH:1](=O)[CH3:2].[CH3:4][O:5][C:6]([C:8]1[CH:9]=[C:10]([CH3:34])[C:11]2[O:17][C:16]3[C:18]([Cl:30])=[CH:19][C:20]([NH:22][CH2:23][CH2:24][N:25]4[CH2:29][CH2:28][CH2:27][CH2:26]4)=[CH:21][C:15]=3[CH2:14][S:13](=[O:32])(=[O:31])[C:12]=2[CH:33]=1)=[O:7].FC(F)(F)C(O)=O.C([BH3-])#N.[Na+]>CO>[CH3:4][O:5][C:6]([C:8]1[CH:9]=[C:10]([CH3:34])[C:11]2[O:17][C:16]3[C:18]([Cl:30])=[CH:19][C:20]([N:22]([CH2:1][CH3:2])[CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][CH2:28][CH2:29]4)=[CH:21][C:15]=3[CH2:14][S:13](=[O:31])(=[O:32])[C:12]=2[CH:33]=1)=[O:7]

Participants

6

Reactant 4

HCID 177AcetaldehydeHCID 6422Trifluoroacetic acidHCID 5003444Sodium cyanoborohydrideHCID 1317284574-Chloro-6-methyl-10,10-dioxo-2-(2-pyrrolidin-1-yl-ethylamino)-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

Product 1

HCID 1317284584-Chloro-2-[ethyl-(2-pyrrolidin-1-yl-ethyl)-amino]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

Distilled acetaldehyde (0.11 mL, 1.90 mmol) was added to a solution of Example 72k (0.180 g, 0.38 mmol) in dry methanol (15 mL), followed by the addition of trifluoroacetic acid (0.03 mL, 0.38 mmol). The reaction mixture was stirred at 0° C. for 2 h. Sodium cyanoborohydride was added and the reaction mixture was allowed to come to room temperature and then left stirring overnight. It was concentrated, treated with 10% aqueous sodium bicarbonate solution, water and extracted with ethyl acetate. The organic layer was washed with water, brine, dried, concentrated and purified using flash chromatography (silica gel, methanol/chloroform) to obtain the title compound as a white solid. Yield: 0.118 g (62%); 1H NMR (DMSO-d6): δ 1.20 (t, 3H, CH3), 1.90-2.00 (m, 4H, 2CH2), 2.60-2-69 (m, 4H, 2CH2), 2.70 (s, 3H, CH3), 3.45 (q, 2H, CH2), 3.55 (t, 2H, CH2), 3.90 (s, 3H, OCH3), 4.70 (s, 2H, CH2), 6.65 (s, 1H, Ar), 6.75 (s, 1H, Ar), 8.10 (s, 1H, Ar), 8.55 (s, 1H, Ar); MS: m/e (ES+) 493 (M+1).

Workup

  1. customto come to room temperature
  2. waitleft
  3. stirringstirring overnight
  4. concentrationIt was concentrated
  5. additiontreated with 10% aqueous sodium bicarbonate solution, water
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with water, brine
  8. customdried
  9. concentrationconcentrated
  10. custompurified

Sources & evidence

ORD record
ord-283b18c179634b6e8c5c417f8fd00d02
Source dataset
uspto-grants-2012_05
Patent number
US08183234B2

Reaction notes

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