Acetic Acid → 4-{3-[2-Fluoro-4-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-phenylamino]-propyl}-tetrahydro-pyran-4-carboxylic acid methyl ester

HRID 1512059Notes

Reaction equation

HRID 1512059 reaction equation
[CH3:1][O:2][C:3]([C:5]1([CH2:11][CH2:12][CH:13]=O)[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)=[O:4].[F:15][C:16]1[CH:21]=[C:20]([N:22]2[CH2:26][CH2:25][C@H:24]([N:27]3[CH2:31][CH2:30][CH2:29][C@@H:28]3[CH3:32])[CH2:23]2)[CH:19]=[CH:18][C:17]=1[NH2:33].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[CH3:1][O:2][C:3]([C:5]1([CH2:11][CH2:12][CH2:13][NH:33][C:17]2[CH:18]=[CH:19][C:20]([N:22]3[CH2:26][CH2:25][C@H:24]([N:27]4[CH2:31][CH2:30][CH2:29][C@@H:28]4[CH3:32])[CH2:23]3)=[CH:21][C:16]=2[F:15])[CH2:6][CH2:7][O:8][CH2:9][CH2:10]1)=[O:4]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 584680574-(3-Oxo-propyl)tetrahydro-pyran-4-carboxylic acid methyl esterHCID 674231022-Fluoro-4-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-phenylamine

Product 1

HCID 584680774-{3-[2-Fluoro-4-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-phenylamino]-propyl}-tetrahydro-pyran-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

4-(3-Oxo-propyl)tetrahydro-pyran-4-carboxylic acid methyl ester (135 mg, 0.515 mmol, 1 eq) was dissolved in 2.4 mL of 1,2-dichloroethane. To this was added 2-Fluoro-4-((2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-phenylamine (103 mg, 0.515 mmol, 1 eq) in 6.2 mL of 1,2-dichloroethane. To the combined mixture was added glacial acetic acid (96 mg, 1.6 mmol, 3.1 eq) followed by NaBH(OAc)3 (330 mg, 1.55 mmol, 3 eq). The reaction mixture was stirred at rt for 15 h. The reaction mixture was quenched with water, transferred to a separatory funnel and extracted with CH-2Cl2 (2×100 mL). The combined organics were dried over Na2SO4, concentrated under vacuum and purified by column chromatography on silica gel (40 g column, 6% MeOH in CH2Cl2; 35 mL/min). This gave 130 mg (61%) of the title compound as a beige semi-solid.

Workup

  1. customThe reaction mixture was quenched with water
  2. customtransferred to a separatory funnel
  3. extractionextracted with CH-2Cl2 (2×100 mL)
  4. dry with materialThe combined organics were dried over Na2SO4
  5. concentrationconcentrated under vacuum
  6. custompurified by column chromatography on silica gel (40 g column, 6% MeOH in CH2Cl2; 35 mL/min)

Sources & evidence

ORD record
ord-6093c12da6dd47d49670b6b95cffdc99
Source dataset
uspto-grants-2012_07
Patent number
US08217052B2

Reaction notes

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