Acetic Acid → HCID 66973000, compound

HRID 1866693Notes

Reaction equation

HRID 1866693 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])C=O.F[C:23]1[CH:24]=C([C@H]2N(CC(OCC)=O)C(=O)C3(CCCC3)NC2)C=[C:27](F)[CH:28]=1.[CH3:47][C:48]([OH:50])=[O:49].[BH3-][C:52]#[N:53].[Na+].[CH3:55]O>>[C:17]([O:16][C:15]([NH:14][C:6]1([CH2:52][NH:53][C:47]2([C:48]([O:50][CH3:55])=[O:49])[CH2:27][CH2:28][CH2:23][CH2:24]2)[C:7]2[C:3](=[C:2]([F:1])[CH:10]=[C:9]([F:11])[CH:8]=2)[CH2:4][CH2:5]1)=[O:21])([CH3:19])([CH3:18])[CH3:20]

Participants

6

Reactant 5

HCID 176Acetic Acid2×HCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 70805595HCID 70805595, compound2×HCID 86616401HCID 86616401, compound

Product 1

HCID 66973000HCID 66973000, compound

Procedure

A mixture of tert-butyl (4,6-difluoro-1-formyl-2,3-dihydro-1H-inden-1-yl)carbamate from Step F (890 mg, 2.99 mmol), methyl 1-aminocyclopentanecarboxylate (4.25 g, 29.7 mmol, described in Intermediate 25), and AcOH (2.10 mL, 36.7 mmol) in MeOH (32 mL) was stirred at ambient temperature for 20 min. NaCNBH3 (405 mg, 6.44 mmol) was added and the pH of the mixture was checked and adjusted to pH ˜5 as necessary by addition of AcOH. The reaction mixture was stirred at ambient temperature for 23 h, then quenched with saturated aqueous NaHCO3 (80 mL) and extracted with EtOAc (200 mL). The organic extract was washed with H2O (50 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with hexane:EtOAc−100:0 to 30:70, to give the title compound. MS: m/z=425 (M+1).

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 23 h
  2. customquenched with saturated aqueous NaHCO3 (80 mL)
  3. extractionextracted with EtOAc (200 mL)
  4. extractionThe organic extract
  5. washwas washed with H2O (50 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with hexane

Sources & evidence

ORD record
ord-64facdbca0bd4ac0b41390e7a2f1aeb2
Source dataset
uspto-grants-2009_12
Patent number
US07629338B2

Reaction notes

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