o-Fluorobenzaldehyde → 4-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid 1-(2-fluoro-benzyl)-pyrrolidin-3-yl ester

HRID 448593Notes

Reaction equation

HRID 448593 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.[NH:10]1[CH2:14][CH2:13][CH:12]([O:15][C:16]([N:18]2[CH2:23][CH2:22][CH:21]([O:24][C:25]3[CH:30]=[C:29]([N:31]4[C:39]5[C:34](=[CH:35][C:36]([S:40]([CH3:43])(=[O:42])=[O:41])=[CH:37][CH:38]=5)[CH2:33][CH2:32]4)[N:28]=[CH:27][N:26]=3)[CH2:20][CH2:19]2)=[O:17])[CH2:11]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][N:10]1[CH2:14][CH2:13][CH:12]([O:15][C:16]([N:18]2[CH2:23][CH2:22][CH:21]([O:24][C:25]3[CH:30]=[C:29]([N:31]4[C:39]5[C:34](=[CH:35][C:36]([S:40]([CH3:43])(=[O:42])=[O:41])=[CH:37][CH:38]=5)[CH2:33][CH2:32]4)[N:28]=[CH:27][N:26]=3)[CH2:20][CH2:19]2)=[O:17])[CH2:11]1

Participants

6

Reactant 3

HCID 67970o-FluorobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 498486594-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid pyrrolidin-3-yl ester

Product 1

HCID 498486614-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid 1-(2-fluoro-benzyl)-pyrrolidin-3-yl ester

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

2-Fluoro-benzaldehyde (11 μL, 0.1 mmol) was dissolved in 1 mL of DCE with 21b (49 mg, 0.1 mmol) and NaBH(OAc)3 (30 mg, 0.14 mmol). The mixture was stirred for 8 h at room temperature then was diluted with DCM and quenched with saturated NaHCO3. The organic layer was washed with saturated NaHCO3 followed by brine. The organic layer was dried, filtered and evaporated. The residue was purified by preparative HPLC to afford 21-1, LCMS 596.2 (MH+).

Workup

  1. customquenched with saturated NaHCO3
  2. washThe organic layer was washed with saturated NaHCO3
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by preparative HPLC
  7. customto afford 21-1, LCMS 596.2 (MH+)

Sources & evidence

ORD record
ord-766c55cf12c249ec8fe5c95858ad4eb6
Source dataset
uspto-grants-2013_07
Patent number
US08481731B2

Reaction notes

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