Acetic Acid → HCID 86660245, compound

HRID 1890712Notes

Reaction equation

HRID 1890712 reaction equation
[NH2:1][C@H:2]([C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[C:15]([F:20])[CH:14]=1)[CH2:3][CH2:4][C:5]([CH3:12])([CH3:11])[C:6]([O:8][CH2:9][CH3:10])=[O:7].[O:21]=[C:22]1[NH:30][C:25]2=[N:26][CH:27]=[CH:28][CH:29]=[C:24]2[C@:23]21[CH2:44][C:33]1[CH:34]=[C:35]3[C:40](=[CH:41][C:32]=1[CH2:31]2)[N:39]=[CH:38][C:37]([CH:42]=O)=[CH:36]3.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl.C(Cl)Cl.C(=O)(O)[O-].[Na+]>[F:20][C:15]1[CH:14]=[C:13]([C@@H:2]([NH:1][CH2:42][C:37]2[CH:38]=[N:39][C:40]3[C:35]([CH:36]=2)=[CH:34][C:33]2[CH2:44][C@:23]4([CH2:31][C:32]=2[CH:41]=3)[C:24]2[C:25](=[N:26][CH:27]=[CH:28][CH:29]=2)[NH:30][C:22]4=[O:21])[CH2:3][CH2:4][C:5]([CH3:11])([CH3:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH:18]=[C:17]([F:19])[CH:16]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 59594304HCID 59594304, compound2×HCID 86660243HCID 86660243, compound

Product 1

HCID 86660245HCID 86660245, compound

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a stirred solution of ethyl (5S)-5-amino-5-(3,5-difluorophenyl)-2,2-dimethylpentanoate from Step A (˜82.0 mg, 0.289 mmol) and (7S)-2′-oxo-1′, 2′,6,8-tetrahydrospiro[cyclopenta[g]quinoline-7,3′-pyrrolo[2,3-b]pyridine]-3-carbaldehyde (91.0 mg, Intermediate 1) in dry chloroform (3 mL) was added HOAc (35 μL, 0.606 mmol). After 10 minutes, sodium triacetoxyborohydride (129 mg, 0.606 mmol) was added. After 80 minutes of stifling, the reaction mixture was diluted with DCM (30 mL) and saturated sodium bicarbonate (20 mL). The layers were separated and the aqueous layer was extracted once with DCM (20 mL). The combined organics were dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue. This residue was applied to a silica gel column for purification, eluting with a gradient of CH2Cl2:MeOH—99:1 to 93:7. Clean product-containing fractions were pooled and concentrated in vacuo to give the title compound, which still contained about 30% of the methyl ester. MS: m/z=585 (M+1).

Workup

  1. waitAfter 80 minutes of stifling
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted once with DCM (20 mL)
  4. dry with materialThe combined organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto provide a residue
  8. customThis residue was applied to a silica gel column for purification
  9. washeluting with a gradient of CH2Cl2
  10. additionClean product-containing fractions
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f0153e01a17e4b56a5fa69be7ba5f2e6
Source dataset
uspto-grants-2013_08
Patent number
US08507477B2

Reaction notes

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