5-Benzyloxyindole → 5-(Benzyloxy)-1H-indol-1-amine

HRID 2217081Notes

Reaction equation

HRID 2217081 reaction equation
NOS(O)(=O)=O.CC(C)([O-])C.[K+].[CH2:13]([O:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][CH:25]=[CH:24]2)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CC(C)([O-])C.[K+].C[N:37]1CCCC1=O.NOS(O)(=O)=O.CN1CCCC1=O>CN1CCCC1=O>[CH2:13]([O:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[N:26]([NH2:37])[CH:25]=[CH:24]2)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

7

Reactant 5

HCID 146245-BenzyloxyindoleHCID 76284hydroxylamine-O-sulfonic acidHCID 23665647Potassium tert-butoxideHCID 86597979HCID 86597979, compound2×HCID 131725956HCID 131725956, compound

Product 1

HCID 149882975-(Benzyloxy)-1H-indol-1-amineYield 953.5%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent3×

Procedure

A solution of 5.3 kg (5.2 kg corrected for 97% purity) of hydroxylamine-O-sulfonic acid (HOSA) in 19.1 kg of N-methylpyrrolidinone (NMP), is prepared and chilled to 0–5° C. A second solution is prepared from 10.6 kg (10.0 kg corrected for 95% purity) of potassium tert-butoxide and 19.3 kg of NMP. An amination vessel is charged with 5.0 kg (4.7 kg corrected for 94% purity) of 5-benzyloxyindole, 15.5 kg of NMP and an initial charge of 0.4 kg of the potassium tert-butoxide/NMP solution. The HOSA/NMP solution and the remaining potassium tert-butoxide/NMP solution are then simultaneously and proportionally metered into the amination vessel over a period of 166 minutes while maintaining a reaction temperature of 14–29° C. to yield a solution containing 4.3 kg (86.0% yield) of 5-benzyloxy-1H-indol-1-amine as determined by external standard HPLC assay. After adding 105 L water, and cooling to 0–5° C., the mixture is filtered. The filtered solid is partitioned with 63 L n-butyl acetate and 8.5 L water, then filtered. The organic phase is concentrated under reduced pressure to give a solid which contains 3.9 kg (77.4% yield) of 5-benzyloxy-1H-indol-1-amine as determined by external standard HPLC assay.

Workup

  1. temperaturechilled to 0–5° C
  2. temperaturewhile maintaining a reaction temperature of 14–29° C.
  3. customto yield a solution

Sources & evidence

ORD record
ord-396f2bd886f047b1826894ebc0084475
Source dataset
uspto-grants-2006_09
Patent number
US07112682B2

Reaction notes

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