Acetic Acid → HCID 22676840, compound

HRID 1006256Notes

Reaction equation

HRID 1006256 reaction equation
C(O)(=[O:3])C.[BH4-].[Na+].[C:7]([C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([CH:26]=[CH2:27])[CH:24]=3)[N:19]([CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=3)[C:18]=2[C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:13][CH:12]=1)([CH3:10])([CH3:9])[CH3:8]>O1CCCC1>[C:7]([C:11]1[CH:12]=[CH:13][C:14]([C:17]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([CH2:26][CH2:27][OH:3])[CH:24]=3)[N:19]([CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=3)[C:18]=2[C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:15][CH:16]=1)([CH3:8])([CH3:9])[CH3:10]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 4311764Sodium borohydrideHCID 22676769HCID 22676769, compound

Product 1

HCID 22676840HCID 22676840, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Acetic acid (63 μL, 66 mg, 1.1 mmol) was added slowly to a cooled (0° C.) and stirred slurry of sodium borohydride (41.6 mg, 1.10 mmol) in tetrahydrofuran (2 mL). The mixture was stirred for 1 h and then a solution of ethyl 3-(4-tert-butylphenyl)-1-(3-methoxybenzyl)-5-vinyl-1H-indole-2-carboxylate (Example 129, 430 mg, 0.920 mmol) in tetrahydrofuran (5+2 mL rinse) was added. The reaction was stirred overnight and then cooled (0° C.). The reaction was quenched by successive addition of EtOH (6 mL), 6 M aqueous sodium acetate (5 mL) and 27% aqueous hydrogen peroxide (5 mL). The mixture was heated (50° C.) for 1 h and then cooled. The reaction was diluted with water (100 mL) and then extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. Flash chromatography of the residue over silica gel using 30% ethyl acetate/hexane afforded 325 mg (75%) of desired product. The product had: 1H NMR (300 MHz, CDCl3) δ 7.28-7.48 (m, 6 H), 7.15-7.22 (m, 2 H), 6.75 (dd, 1 H), 6.64-6.72 (m, 2 H), 7.76(s, 2 H), 4.08 (q, 2 H), 3.78-4.00 (m, 3 H), 3.73 (s, 3 H), 2.91 (t, 2 H), 1.39 (s, 9 H), 0.95 (t, 3 H).

Workup

  1. stirringThe reaction was stirred overnight
  2. temperaturecooled (0° C.)
  3. customThe reaction was quenched by successive addition of EtOH (6 mL), 6 M aqueous sodium acetate (5 mL) and 27% aqueous hydrogen peroxide (5 mL)
  4. temperatureThe mixture was heated (50° C.) for 1 h
  5. temperaturecooled
  6. additionThe reaction was diluted with water (100 mL)
  7. extractionextracted with ethyl acetate (3×50 mL)
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9b94563cae4347259b0cdde32852024f
Source dataset
uspto-grants-2004_09
Patent number
US06787651B2

Reaction notes

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