Sodium triacetoxyborohydride → (2-{[3-Iodo-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-ylmethyl]-methylamino}-ethyl)-methyl-carbamic acid tert-butyl ester

HRID 2167406Notes

Reaction equation

HRID 2167406 reaction equation
[I:1][C:2]1[C:6]([CH:7]=O)=[CH:5][N:4]([CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[N:3]=1.[CH3:15][N:16]([CH2:24][CH2:25][NH:26][CH3:27])[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C.ClCCl>[I:1][C:2]1[C:6]([CH2:7][N:26]([CH3:27])[CH2:25][CH2:24][N:16]([CH3:15])[C:17](=[O:23])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[CH:5][N:4]([CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[N:3]=1

Participants

6

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 14403871tert-Butyl methyl(2-(methylamino)ethyl)carbamateHCID 904242893-Iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-4-carbaldehyde

Product 1

HCID 90433930(2-{[3-Iodo-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-ylmethyl]-methylamino}-ethyl)-methyl-carbamic acid tert-butyl esterYield 92.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

A mixture of 3-iodo-1-(oxan-2-yl)-1H-pyrazole-4-carbaldehyde (21.5 g, 70.24 mmol, 1.00 equiv), tert-butyl N-methyl-N-(2-(methylamino)ethyl)carbamate (20 g, 106.23 mmol, 1.51 equiv) and NaBH(OAc)3 (29.8 g, 137.98 mmol, 1.96 equiv) in dichloroethane (300 mL) was stirred for 1 h at room temperature. The reaction was diluted with 300 mL of dichloromethane and then washed with 3×300 mL of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with 0-7% methanol in dichloromethane to give 31 g (92%) of tert-butyl (2-(((3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)methyl)(methyl)amino)ethyl)(methyl)carbamate as a yellow oil. 1H NMR (300 MHz, CDCl3): δ 7.62 (s, 1H), 5.34-5.30 (m, 1H), 4.06-4.02 (m, 1H), 3.68-3.62 (m, 1H), 3.42-3.38 (m, 4H), 2.85 (s, 4H), 2.62-2.53 (m, 2H), 2.47-2.46 (m, 2H), 2.13-1.97 (m, 3H), 1.74-1.69 (m, 3H), 1.46 (s, 9H) ppm. LCMS (method A, ESI): RT=1.17 min, m/z=479.0 [M+H]+.

Workup

  1. washwashed with 3×300 mL of brine
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified on a silica gel column
  5. washeluted with 0-7% methanol in dichloromethane

Sources & evidence

ORD record
ord-09aeb2a767bf417bba4d904879269a8c
Source dataset
uspto-grants-2015_06
Patent number
US09045455B2

Reaction notes

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