2,2-Dimethoxypropane → HCID 66953584, compound

HRID 390067Notes

Reaction equation

HRID 390067 reaction equation
[OH:1][CH2:2][C:3]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])([CH2:6][OH:7])[CH2:4][OH:5].CO[C:17](OC)([CH3:19])[CH3:18].C(OCC)(=O)C>CN(C=O)C.C(OCC)C.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>[OH:1][CH2:2][C:3]1([NH:8][C:9](=[O:14])[C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:6][O:7][C:17]([CH3:19])([CH3:18])[O:5][CH2:4]1

Participants

7

Reactant 3

HCID 64952,2-DimethoxypropaneHCID 8857Ethyl AcetateHCID 18737286HCID 18737286, compound

Product 1

HCID 66953584HCID 66953584, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)CatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 2-amino-2-(hydroxymethyl)propane-1,3-diol (15.7 g, 130 mmol) and di-tert-butyl dicarbonate (31.1 g, 143 mmol) in methanol (400 mL) and water (40 mL) was stirred at ambient temperature for 72 h. The contents of the flask were evaporated and the resulting white solid dissolved in minimal hot ethyl acetate and allowed to recrystallise overnight. The crystals were filtered and washed with petroleum ether to give N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)pivalamide (26.5 g, 130 mmol, 100%) as fluffy, white needles. To a solution of N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)pivalamide (9.50 g, 42.0 mmol) and 2,2-dimethoxypropane (16.0 mL, 129 mmol) in DMF (100 mL) was added pyridinium para-toluenesulfonate (0.540 g, 2.15 mmol) at RT. The reaction was stirred at ambient temperature for 15 h. after which time the reaction was complete by TLC (petroleum ether:ethyl acetate, 4:1, visualised with Erlichs). The reaction mixture was diluted with diethyl ether, washed three times with aqueous sodium bicarbonate, once with brine, dried over magnesium sulphate, filtered and evaporated. The resulting semi-solid was recrystallised from minimal hot petroleum ether to give N-(5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxan-5-yl)pivalamide (7.32 g, 65%) as white crystals. 1H NMR (CDCl3) δ 5.31 (br s, 1H, NH), 4.18 (br s, 1H, OH), 3.85 (d, J=11.5 Hz, 2H), 3.80 (d, J=11.5 Hz, 2H), 3.70 (d, 6.6 Hz, 2H), 1.46 (s, 12H), 1.44 (s, 3H). 13C NMR (CDCl3) δ 154.0, 98.8, 80.5, 64.8, 64.5 (2C), 53.4, 28.3 (3C), 26.9, 20.3.

Workup

  1. washwashed three times with aqueous sodium bicarbonate
  2. dry with materialonce with brine, dried over magnesium sulphate
  3. filtrationfiltered
  4. customevaporated
  5. customThe resulting semi-solid was recrystallised from minimal hot petroleum ether

Sources & evidence

ORD record
ord-6c59c021574642928e0b7187fc824e6e
Source dataset
uspto-grants-2013_02
Patent number
US08383636B2

Reaction notes

Loading…