Isopropyl Acetate → N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-(1-methyl-1H-pyrazol-4-yl)phenethoxy)propanamide

HRID 909886Notes

Reaction equation

HRID 909886 reaction equation
[CH3:1][O:2][CH:3]([O:12][CH3:13])[CH2:4][NH:5][CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.[CH3:14][N:15]1[CH:19]=[C:18]([C:20]2[CH:21]=[C:22]([CH:31]=[CH:32][CH:33]=2)[CH2:23][CH2:24][O:25][CH2:26][CH2:27][C:28](O)=[O:29])[CH:17]=[N:16]1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.C(=O)(O)[O-].[Na+].C(OC(C)C)(=O)C>O1CCCC1.C(N(CC)CC)C>[CH:6]1([N:5]([CH2:4][CH:3]([O:12][CH3:13])[O:2][CH3:1])[C:28](=[O:29])[CH2:27][CH2:26][O:25][CH2:24][CH2:23][C:22]2[CH:31]=[CH:32][CH:33]=[C:20]([C:18]3[CH:17]=[N:16][N:15]([CH3:14])[CH:19]=3)[CH:21]=2)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1

Participants

8

Reactant 5

HCID 7915Isopropyl AcetateHCID 111923Propylphosphonic anhydrideHCID 516892Sodium BicarbonateHCID 3024915N-(2,2-dimethoxyethyl)cyclohexanamineHCID 592904613-(3-(1-methyl-1H-pyrazol-4-yl)phenethoxy)propanoic acid

Product 1

HCID 59290438N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-(1-methyl-1H-pyrazol-4-yl)phenethoxy)propanamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent4×HCID 8471TriethylamineSolvent

Conditions

Temperature
20 °C

Procedure

A solution of N-(2,2-dimethoxyethyl)cyclohexanamine (21.5 g) in tetrahydrofuran (30 mL) was added to a solution of 3-(3-(1-methyl-1H-pyrazol-4-yl)phenethoxy)propanoic acid in tetrahydrofuran (105 mL) at 20° C. Tetrahydrofuran (15 mL) was added, followed by triethylamine (51.8 mL), followed by a solution of T3P in tetrahydrofuran (121.9 mL of a 1.62M solution). The solution was stirred at 20° C. for 1 h then cooled to 10° C. Pre-chilled (10° C.) 0.5M sodium bicarbonate solution (225 mL) was added, followed by iso-propyl acetate (150 mL). After mixing the layers were separated and the organic layer washed with 20% w/w sodium chloride solution (150 mL), then evaporated to dryness to afford the subtitled compound as a brown oil (48.6 g). MS [M+H-MeOH]+=412.20 (100%) (MultiMode+) [M+H]+=444.20 (MultiMode+) 1H NMR (300 MHz, CDCl3) δ 7.75 (s, 1H), 7.62 (s, 1H), 7.33-7.23 (m, 3H), 7.10-7.03 (m, 1H), 4.61 (t, 0.7H), 4.36 (t, 0.3H), 3.94 (s, 3H), 3.79 (q, 2H), 3.69 (q, 2H), 3.62-3.43 (m, 1.5H), 3.40 (s, 3H), 3.38 (s, 3H), 3.30 (d, 1.5H), 2.89 (q, 2H), 2.69 (quintet, 2H), 1.86-0.99 (m, 10H); approx:2:1 ratio of rotamers

Workup

  1. temperaturethen cooled to 10° C
  2. additionwas added
  3. additionAfter mixing the layers
  4. customwere separated
  5. washthe organic layer washed with 20% w/w sodium chloride solution (150 mL)
  6. customevaporated to dryness

Sources & evidence

ORD record
ord-c0e53257ee404059834e42fa956a387b
Source dataset
uspto-grants-2011_09
Patent number
US08017602B2

Reaction notes

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