Sodium borohydride → (S)-3-(1,1-Difluoro-2-hydroxyethyl)-1'-((2-(trimethylsilyl)ethoxy)methyl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

HRID 588731Notes

Reaction equation

HRID 588731 reaction equation
[F:1][C:2]([F:34])([C:8]1[CH:9]=[C:10]2[CH2:33][C@@:15]3([C:23]4[C:18](=[N:19][CH:20]=[CH:21][CH:22]=4)[N:17]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:16]3=[O:32])[CH2:14][C:11]2=[N:12][CH:13]=1)[C:3](OCC)=[O:4].[Cl-].[Ca+2].[Cl-].[BH4-].[Na+]>CO>[F:34][C:2]([C:8]1[CH:9]=[C:10]2[CH2:33][C@@:15]3([C:23]4[C:18](=[N:19][CH:20]=[CH:21][CH:22]=4)[N:17]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:29])([CH3:31])[CH3:30])[C:16]3=[O:32])[CH2:14][C:11]2=[N:12][CH:13]=1)([F:1])[CH2:3][OH:4]

Participants

5

Reactant 3

HCID 4311764Sodium borohydrideHCID 5284359Calcium ChlorideHCID 131734437(S)-Ethyl 2,2-difluoro-2-(2'-oxo-1'-((2-(trimethylsilyl)ethoxy)methyl)-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-3-yl)acetate

Product 1

HCID 90064628(S)-3-(1,1-Difluoro-2-hydroxyethyl)-1'-((2-(trimethylsilyl)ethoxy)methyl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (S)-ethyl 2,2-difluoro-2-(2′-oxo-1′-((2-(trimethylsilyl)ethoxy)methyl)-1′,2′,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridin]-3-yl)acetate (0.542 g, 1.11 mmol) in MeOH (10 mL) at ambient temperature was added calcium chloride (0.184 g, 1.66 mmol) and sodium borohydride (0.128 g, 3.32 mmol). After stirring at ambient temperature for 24 h, the reaction was quenched with a saturated solution of sodium chloride (5 mL), partitioned between water (20 mL) and EtOAc (100 mL). The organic layer was removed and the aqueous phase was extracted further with EtOAc (30 mL). The combined organic extracts were washed with brine, then dried over sodium sulfate, filtered, and concentrated to dryness in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH—100:0 to 93:7, to give the title compound. MS: m/z=448.1 (M+1).

Workup

  1. customthe reaction was quenched with a saturated solution of sodium chloride (5 mL)
  2. custompartitioned between water (20 mL) and EtOAc (100 mL)
  3. customThe organic layer was removed
  4. extractionthe aqueous phase was extracted further with EtOAc (30 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness in vacuo
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-269d8e97080f43a8a2a49b50b90577dd
Source dataset
uspto-grants-2016_01
Patent number
US09227972B2

Reaction notes

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