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Through his mother, Barclay inherited a share in the Freame Bank, the oldest surviving Quaker bank in London.
1767 Barclay married his second wife, Rachel, daughter of Sampson Lloyd (1699-1779), banker.
1776 he became an active partner in the Freame Bank, by then styled Barclay, Bevan, and Bening which developed as the Lombard Street node of a network of Quaker country bankers, financing bridges and canals as well as trading enterprises.
After many changes of partners, with the Barclays, Bevans, and Trittons predominating, this firm became the nucleus of the corporate merger of 1896 which became Barclay and Co. Ltd.
1781 Barclay and his nephews, Robert Barclay and Silvanus Bevan, bought the Anchor Brewery in Southwark from Mrs Hester Thrale. This became Barclay, Perkins and Co., one of the three great London breweries of the nineteenth century.
By 1783 David and his brother John, who were partners in their father's linen and merchant house in Cheapside, decided to wind up the linen business because of the changes in the business environment as a result of the American War of Independence.
The later partnership records of the bank suggest that he became a sleeping partner at some time in the 1780s.