Dichloromethane → 5-Hydroxymethyl-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester

HRID 1486499Notes

Reaction equation

HRID 1486499 reaction equation
[CH2:1]([OH:4])[C:2]#[CH:3].[CH2:5]([O:12][C:13](=[O:21])[N:14]([CH2:18][C:19]#[CH:20])[CH2:15][C:16]#[CH:17])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C(Cl)Cl>C1(C)C=CC=CC=1>[CH2:5]([O:12][C:13]([N:14]1[CH2:18][C:19]2[C:16](=[CH:17][CH:3]=[C:2]([CH2:1][OH:4])[CH:20]=2)[CH2:15]1)=[O:21])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 7859Propargyl alcoholHCID 14358054benzyl N,N-bis(prop-2-yn-1-yl)carbamate

Product 1

HCID 579902105-Hydroxymethyl-1,3-dihydro-isoindole-2-carboxylic acid benzyl esterYield 113%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
55 °C

Procedure

A solution of propargyl alcohol (2.11 Kg, 37.7 mol) in toluene (32.48 L) was degassed and heated to 55° C. The solution of di-prop-2-ynyl-carbamic acid benzyl ester (4.06 Kg, 17.86 mol, step 6) in toluene and Wilkinsons catalyst (0.162 Kg) were added in 10 equal portions such that temperature <65° C. (the exotherm was allowed to subside before the next addition was made). The solution was then stirred at 55° C. for 1 h and then cooled to 20° C. DCM (8.12 L) was added and the mixture was concentrated to a small volume. Toluene (8 L) was added and the solution evaporated to constant weight giving the title compound 5.72 Kg (113%).

Workup

  1. additionwere added in 10 equal portions such that temperature <65° C. (the exotherm
  2. additionto subside before the next addition
  3. temperaturecooled to 20° C
  4. concentrationthe mixture was concentrated to a small volume
  5. additionToluene (8 L) was added
  6. customthe solution evaporated to constant weight

Sources & evidence

ORD record
ord-23093cd026af4215a36e9885295c1798
Source dataset
uspto-grants-2016_08
Patent number
US09428439B2

Reaction notes

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