Methanol → (3S,7S)-Octahydro-1-(phenylmethyl)-5-(phenylsulfonyl)-1,5-diazocine-3,7-diol

HRID 2078434Notes

Reaction equation

CO.[O:3]1[CH2:5][C@H:4]1[CH2:6][N:7]([CH2:17][C@@H:18]1[CH2:20][O:19]1)[S:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)(=[O:10])=[O:9].[CH2:21]([NH2:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>ClC1C=CC=CC=1>[CH2:21]([N:28]1[CH2:5][C@H:4]([OH:3])[CH2:6][N:7]([S:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)(=[O:10])=[O:9])[CH2:17][C@@H:18]([OH:19])[CH2:20]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

Conditions

Temperature: 65 °C

Procedure

Methanol (2494 kg, 18 rel. vol.—either fresh or recycled) was charged to a reaction vessel and heated to reflux temperature (approx. 65° C.). Simultaneously, and over approximately 6 hours were charged the chlorobenzene solution (containing chirally enriched N,N-bis(2(R)-oxiranylmethyl)benzenesulfonamide) from step (i), Alternative 2 above and benzylamine (109 kg, 0.91 eq.). The batch was maintained at reflux throughout the addition. The reaction was stirred at approximately 65° C. (reflux temperature) for a further 3 hours. Methanol (1938 kg, 14 rel. vol.) was then removed by distillation at atmospheric pressure before chlorobenzene (775 kg, 4 rel. vol.) was added. The resulting solution was used without further treatment in the next step (see step (iii), Alternative 2 below).

Workup

temperatureheated
temperatureThe batch was maintained
temperatureat reflux throughout the addition
temperature(reflux temperature) for a further 3 hours
customMethanol (1938 kg, 14 rel. vol.) was then removed by distillation at atmospheric pressure before chlorobenzene (775 kg, 4 rel. vol.)
additionwas added

Sources & evidence

ORD record: ord-1a52f81440d04b8c9a57c49ee4c2545f
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07928225B2

Reaction notes

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